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  • 1.
    Bauzá-Thorbrügge, Marco
    et al.
    Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Peris, Eduard
    Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Zamani, Shabnam
    Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Micallef, Peter
    Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Paul, Alexandra
    Department of Biology and Biological Engineering, Division of Chemical Biology, Chalmers University of Technology, Gothenburg, Sweden ; The Department of Biomedical Engineering, University of Texas at Austin, TX, United States.
    Bartesaghi, Stefano
    Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Wernstedt Asterholm, Ingrid
    Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    NRF2 is essential for adaptative browning of white adipocytes2023Inngår i: Redox Biology, E-ISSN 2213-2317, Vol. 68, artikkel-id 102951Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes. 

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  • 2.
    Bauzá-Thorbrügge, Marco
    et al.
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Vujičić, Milica
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Chanclón, Belén
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Palsdottir, Vilborg
    Unit for Endocrine Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Pillon, Nicolas J.
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Wernstedt Asterholm, Ingrid
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Adiponectin stimulates Sca1+CD34-adipocyte precursor cells associated with hyperplastic expansion and beiging of brown and white adipose tissue2024Inngår i: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 151, artikkel-id 155716Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The adipocyte hormone adiponectin improves insulin sensitivity and there is an inverse correlation between adiponectin levels and type-2 diabetes risk. Previous research shows that adiponectin remodels the adipose tissue into a more efficient metabolic sink. For instance, mice that overexpress adiponectin show increased capacity for hyperplastic adipose tissue expansion as evident from smaller and metabolically more active white adipocytes. In contrast, the brown adipose tissue (BAT) of these mice looks “whiter” possibly indicating reduced metabolic activity. Here, we aimed to further establish the effect of adiponectin on adipose tissue expansion and adipocyte mitochondrial function as well as to unravel mechanistic aspects in this area. Methods: Brown and white adipose tissues from adiponectin overexpressing (APN tg) mice and littermate wildtype controls, housed at room and cold temperature, were studied by histological, gene/protein expression and flow cytometry analyses. Metabolic and mitochondrial functions were studied by radiotracers and Seahorse-based technology. In addition, mitochondrial function was assessed in cultured adiponectin deficient adipocytes from APN knockout and heterozygote mice. Results: APN tg BAT displayed increased proliferation prenatally leading to enlarged BAT. Postnatally, APN tg BAT turned whiter than control BAT, confirming previous reports. Furthermore, elevated adiponectin augmented the sympathetic innervation/activation within adipose tissue. APN tg BAT displayed reduced metabolic activity and reduced mitochondrial oxygen consumption rate (OCR). In contrast, APN tg inguinal white adipose tissue (IWAT) displayed enhanced metabolic activity. These metabolic differences between genotypes were apparent also in cultured adipocytes differentiated from BAT and IWAT stroma vascular fraction, and the OCR was reduced in both brown and white APN heterozygote adipocytes. In both APN tg BAT and IWAT, the mesenchymal stem cell-related genes were upregulated along with an increased abundance of Lineage−Sca1+CD34− “beige-like” adipocyte precursor cells. In vitro, the adiponectin receptor agonist Adiporon increased the expression of the proliferation marker Pcna and decreased the expression of Cd34 in Sca1+ mesenchymal stem cells. Conclusions: We propose that the seemingly opposite effect of adiponectin on BAT and IWAT is mediated by a common mechanism; while reduced adiponectin levels are linked to lower adipocyte OCR, elevated adiponectin levels stimulate expansion of adipocyte precursor cells that produce adipocytes with intrinsically higher metabolic rate than classical white but lower metabolic rate than classical brown adipocytes. Moreover, adiponectin can modify the adipocytes' metabolic activity directly and by enhancing the sympathetic innervation within a fat depot. 

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  • 3.
    Benrick, Anna
    et al.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Chanclón, Belén
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Micallef, Peter
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Wu, Yanling
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hadi, Laila
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Shelton, John M.
    Molecular Pathology Core, University of Texas Southwestern Medical Center, Dallas, TX, USA.
    Stener-Victorin, Elisabet
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Wernstedt Asterholm, Ingrid
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Adiponectin protects against development of metabolic disturbances in a PCOS mouse model2017Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, nr 34, s. E7187-E7196, artikkel-id 201708854Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adiponectin, together with adipocyte size, is the strongest factor associated with insulin resistance in women with polycystic ovary syndrome (PCOS). This study investigates the causal relationship between adiponectin levels and metabolic and reproductive functions in PCOS. Prepubertal mice overexpressing adiponectin from adipose tissue (APNtg), adiponectin knockouts (APNko), and their wild-type (WT) littermate mice were continuously exposed to placebo or dihydrotestosterone (DHT) to induce PCOS-like traits. As expected, DHT exposure led to reproductive dysfunction, as judged by continuous anestrus, smaller ovaries with a decreased number of corpus luteum, and an increased number of cystic/atretic follicles. A two-way between-groups analysis showed that there was a significant main effect for DHT exposure, but not for genotype, indicating adiponectin does not influence follicle development. Adiponectin had, however, some protective effects on ovarian function. Similar to in many women with PCOS, DHT exposure led to reduced adiponectin levels, larger adipocyte size, and reduced insulin sensitivity in WTs. APNtg mice remained metabolically healthy despite DHT exposure, while APNko-DHT mice were even more insulin resistant than their DHT-exposed littermate WTs. DHT exposure also reduced the mRNA expression of genes involved in metabolic pathways in gonadal adipose tissue of WT and APNko, but this effect of DHT was not observed in APNtg mice. Moreover, APNtg-DHT mice displayed increased pancreatic mRNA levels of insulin receptors, Pdx1 and Igf1R, suggesting adiponectin stimulates beta cell viability/hyperplasia in the context of PCOS. In conclusion, adiponectin improves metabolic health but has only minor effects on reproductive functions in this PCOS-like mouse model.

  • 4.
    Benrick, Anna
    et al.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kokosar, Milana
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hu, Min
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Larsson, Martin
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Maliqueo, Manuel
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Marcondes, Rodrigo Rodrigues
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Disciplina de Ginecologia, Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Soligo, Marzia
    Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche, Rome, Italy.
    Protto, Virginia
    Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche, Rome, Italy.
    Jerlhag, Elisabet
    Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sazonova, Antonina
    Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Behre, Carl Johan
    Department of Cardiology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Højlund, Kurt
    Department of Endocrinology, Odense University Hospital, Odense, Denmark.
    Thorén, Peter
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture2017Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 31, nr 8, s. 3288-3297Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of alpha-/beta-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.

  • 5.
    Benrick, Anna
    et al.
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Pillon, Nicolas J.
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Nilsson, Emma
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    Lindgren, Eva
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Krook, Anna
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Ling, Charlotte
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Electroacupuncture mimics exercise-induced changes in skeletal muscle gene expression in women with polycystic ovary syndrome2020Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, nr 6, s. 2027-2041Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context

    Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown.

    Objective

    To identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS).

    Design/Participants

    In a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays.

    Results

    A single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q < 0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q < 0.20), and these changes correlated with altered expression of 101 genes (P < 0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these 2 genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis.

    Conclusion

    Our findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.

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  • 6.
    Boberg, Lena
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Szekeres, Ferenc L. M.
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande.
    Arner, Anders
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Signaling and metabolic properties of fast and slow smooth muscle types from mice2018Inngår i: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 470, nr 4, s. 681-691Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study aims to improve the classification of smooth muscle types to better understand their normal and pathological functional phenotypes. Four different smooth muscle tissues (aorta, muscular arteries, intestine, urinary bladder) with a 5-fold difference in maximal shortening velocity were obtained from mice and classified according to expression of the inserted myosin heavy chain (SMHC-B). Western blotting and quantitative PCR analyses were used to determine 15 metabolic and 8 cell signaling key components in each tissue. The slow muscle type (aorta) with a 12 times lower SMHC-B had 6-fold lower expression of the phosphatase subunit MYPT1, a 7-fold higher expression of Rhokinase 1, and a 3-fold higher expression of the PKC target CPI17, compared to the faster (urinary bladder) smooth muscle. The slow muscle had higher expression of components involved in glucose uptake and glycolysis (type 1 glucose transporter, 3 times; hexokinase, 13 times) and in gluconeogenesis (phosphoenolpyruvate carboxykinase, 43 times), but lower expression of the metabolic sensing AMP-activated kinase, alpha 2 isoform (5 times). The slow type also had higher expression of enzymes involved in lipid metabolism (hormone-sensitive lipase, 10 times; lipoprotein lipase, 13 times; fatty acid synthase, 6 times; type 2 acetyl-coenzyme A carboxylase, 8 times). We present a refined division of smooth muscle into muscle types based on the analysis of contractile, metabolic, and signaling components. Slow compared to fast smooth muscle has a lower expression of the deactivating phosphatase and upregulated Ca2+ sensitizing pathways and is more adapted for sustained glucose and lipid metabolism. © 2018 The Author(s)

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  • 7.
    Borgström, Juliana
    Högskolan i Skövde, Institutionen för biovetenskap.
    Cyclical Women: Menstrual Cycle Effects on Mood and Neuro-Cognitive Performance2019Independent thesis Basic level (degree of Bachelor), 15 poäng / 22,5 hpOppgave
    Abstract [en]

    During roughly forty years of a woman’s life-span, the fertile female human body prepares itself monthly for the possibility of pregnancy. Science has shown that the fluctuation of the sex steroids progesterone and estrogen have a crucial role in the female body's physiology, determining the menstrual cycle and its general phases. This biological dance of hormones governing the cycle influences a lot of physical, mental and cognitive aspects of life for a fertile ovulating woman. Although the question of whether these changes also affect women's cognitive performance is still unclear, some evidence has been gathered that could bring us closer to answers. Recent research findings show that this hormonal interplay might have a significant role in cognitive and psychological development - modulating brain activity, cognitive performance, higher cognition, emotional status, sensory processing, appetite and more. This thesis aims to uncover to what extent the menstrual cycle affects brain functions, neurobiology, mood, well-being and cognitive performance in menstruating cisgender women.

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  • 8.
    Ekström, Anette
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Widström, Ann-Marie
    Department of Woman and Child Health, Division of Reproductive and Perinatal Health Care, Karolinska Institutet, Stockholm, Sweden.
    Nissen, Eva
    Högskolan i Skövde, Institutionen för vård och natur.
    Duration of Breastfeeding in Swedish Primiparous and Multiparous Women2003Inngår i: Journal of Human Lactation, ISSN 0890-3344, E-ISSN 1552-5732, Vol. 19, nr 2, s. 172-178Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to describe the effects of sociodemographicfactors and maternity ward practices on the duration of breastfeedingin Swedish primiparas (n = 194) and multiparas (n = 294), consecutivelyselected from hospital birth files for 3 months, who respondedto a questionnaire 9 to 12 months after childbirth. The impactof sociodemographic data and maternity ward practices on exclusiveand any breastfeeding were examined. Smoking and supplementationwithout medical reasons influenced the duration of both exclusiveand any breastfeeding negatively, whereas early first breastfeedinginfluenced the duration of both exclusive and any breastfeedingpositively, and parity had no significant influence. Late hospitaldischarge influenced the duration of exclusive breastfeedingpositively, and higher maternal age influenced the durationof any breastfeeding positively. These variables altogetherexplained 11.4% (P <.001) of the variance in the durationof exclusive breastfeeding and 8.2% (P <.001) of the durationof any breastfeeding

  • 9.
    Fornes, Romina
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Maliqueo, Manuel
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Endocrinology and Metabolism Laboratory, Department of Medicine, West Division, University of Chile, Santiago, Chile.
    Hu, Min
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Hadi, Laila
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jimenez-Andrade, Juan M.
    Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, Mexico.
    Ebefors, Kerstin
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nyström, Jenny
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Labrie, Fernand
    Laval University Research Center in Molecular Endocrinology, Oncology and Human Genomics, CHUL Research Center, Quebec, Canada.
    Jansson, Thomas
    Department of Obstetrics & Gynecology, Division of Reproductive Sciences, University Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden.
    The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams2017Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikkel-id 8066Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

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  • 10.
    Fornes, Romina
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna.
    Qi, Xiaojuan
    Department of Physiology, Qiqihar Medical University, Qiqihar, China.
    Vorontsov, Egor
    Proteomics Core Facility, University of Gothenburg, Gothenburg.
    Sihlbom, Carina
    Proteomics Core Facility, University of Gothenburg, Gothenburg.
    Nyström, Jenny
    Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Jerlhag, Elisabet
    Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Maliqueo, Manuel
    Endocrinology and Metabolism, Faculty of Medicine, West division, University of Chile, Santiago, Chile.
    Hirschberg, Angelica Lindén
    Division of Obstetrics and Gynecology, Karolinska University Hospital, Solna.
    Carlström, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Solna.
    Mice exposed to maternal androgen excess and diet-induced obesity have altered phosphorylation of catechol-O-methyltransferase in the placenta and fetal liver2019Inngår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, s. 2176-2188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/objectives: Maternal obesity together with androgen excess in mice negatively affects placental function and maternal and fetal liver function as demonstrated by increased triglyceride content with dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage. To identify changes in molecular pathways that might promote diseases in adulthood, we performed a global proteomic analysis using a liquid-chromatography/mass-spectrometry system to investigate total and phosphorylated proteins in the placenta and fetal liver in a mouse model that combines maternal obesity with maternal androgen excess. Methods: After ten weeks on a control diet (CD) or high fat/high sugar-diet, dams were mated with males fed the CD. Between gestational day (GD) 16.5 and GD 18.5, mice were injected with vehicle or dihydrotestosterone (DHT) and sacrificed at GD 18.5 prior to dissection of the placentas and fetal livers. Four pools of female placentas and fetal livers were subjected to a global proteomic analysis. Total and phosphorylated proteins were filtered by ANOVA q < 0.05, and this was followed by two-way ANOVA to determine the effect of maternal obesity and/or androgen exposure. Results: In placenta, phosphorylated ATP-citrate synthase was decreased due to maternal obesity, and phosphorylated catechol-O-methyltransferase (COMT) was differentially expressed due to the interaction between maternal diet and DHT exposure. In fetal liver, five total proteins and 48 proteins phosphorylated in one or more sites, were differentially expressed due to maternal obesity or androgen excess. In fetal liver, phosphorylated COMT expression was higher in fetus exposed to maternal obesity. Conclusion: These results suggest a common regulatory mechanism of catecholamine metabolism in the placenta and the fetal liver as demonstrated by higher phosphorylated COMT expression in the placenta and fetal liver from animals exposed to diet-induced maternal obesity and lower expression of phosphorylated COMT in animals exposed to maternal androgen excess. © 2019, Springer Nature Limited.

  • 11.
    Fritz, T.
    et al.
    Center for Family and Community Medicine, Karolinska Institutet, Huddinge, Sweden.
    Caidahl, K.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Krook, A.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lundström, P.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mashili, F.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Osler, M.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Szekeres, Ferenc L. M.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Östenson, C. G.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Wändell, P.
    Center for Family and Community Medicine, Karolinska Institutet, Huddinge, Sweden.
    Zierath, J. R.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Effects of Nordic walking on cardiovascular risk factors in overweight individuals with type 2 diabetes, impaired or normal glucose tolerance2013Inngår i: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 29, nr 1, s. 25-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Physical activity remains a valuable prevention for metabolic disease. The effects of Nordic walking on cardiovascular risk factors were determined in overweight individuals with normal or disturbed glucose regulation. Methods We included 213 individuals, aged 60 +/- 5.3 years and with body mass index (BMI) of 30.2 +/- 3.8 kg/m(2); of these, 128 had normal glucose tolerance (NGT), 35 had impaired glucose tolerance (IGT) and 50 had type 2 diabetes mellitus (T2DM). Participants were randomized to unaltered physical activity or to 5 h per week of Nordic walking with poles, for a 4-month period. Dietary habits were unaltered. BMI, waist circumference, blood pressure, glucose tolerance, clinical chemistry, maximal oxygen uptake (peak VO2) and self-reported physical activity (questionnaire) were assessed at the time of inclusion and after 4 months. The participants in the exercise-intervention group kept a walking diary. Results In the NGT exercise group, self-reported physical activity increased markedly, and body weight (-2.0 +/- 3.8 kg), BMI (-0.8 +/- 1.4 kg/m(2)) and waist circumference (- 4.9 +/- 4.4 cm) (mean +/- SD) decreased. Exercise power output (12.9 +/- 9.9 W) and peak VO2 (2.7 +/- 2.8 mL/kg/min) increased in the IGT exercise group. More cardiovascular risk factors were improved after exercise intervention in people with NGT compared with those with IGT or T2DM. Exercise capacity improved significantly in all three groups of participants who reported at least 80% compliance with the scheduled exercise. Conclusions Nordic walking improved anthropometric measurements and exercise capacity. However, unsupervised Nordic walking may not provide a sufficient increase in exercise intensity to achieve ultimate health-promoting benefits on the cardiovascular parameters assessed in this study, particularly for those with disturbed glucose regulation. Copyright (C) 2012 John Wiley & Sons, Ltd.

  • 12.
    Hellström Muhli, Ulla
    Högskolan i Skövde, Institutionen för vård och natur.
    Refining the analytic lens to study elderly pain2008Inngår i: HCRC Newsletter, nr 5, s. 4-4Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 13.
    Huang-Doran, Isabel
    et al.
    Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
    Bicknell, Louise S.
    Medical Research Council Human Genetics Unit, Institute of Genetics and Mo- lecular Medicine, Western General Hospital, Edinburgh, UK.
    Finucane, Francis M.
    Metabolic Research Unit, St. James Hospital, Trinity College, Dublin, Ireland.
    Rocha, Nuno
    Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
    Porter, Keith M.
    Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
    Tung, Y. C. Loraine
    Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
    Szekeres, Ferenc
    Integrative Physiology, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Krook, Anna
    Integrative Physiology, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Nolan, John J.
    Metabolic Research Unit, St. James Hospital, Trinity College, Dublin, Ireland.
    O'Driscoll, Mark
    Human DNA Damage Response Disorders Group, University of Sussex, Brighton, UK.
    Bober, Michael
    Division of Genetics, Department of Pediatrics, Alfred I. DuPont Hospital for Children, Wilmington, Delaware.
    O'Rahilly, Stephen
    Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
    Jackson, Andrew P.
    Medical Research Council Human Genetics Unit, Institute of Genetics and Mo- lecular Medicine, Western General Hospital, Edinburgh, UK.
    Semple, Robert K.
    Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
    Genetic Defects in Human Pericentrin Are Associated With Severe Insulin Resistance and Diabetes2011Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, nr 3, s. 925-935Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE-Genetic defects in human pericentrin (PCNT), encoding the centrosomal protein pericentrin, cause a form of osteodysplastic primordial dwarfism that is sometimes reported to be associated with diabetes. We thus set out to determine the prevalence of diabetes and insulin resistance among patients with PCNT defects and examined the effects of pericentrin depletion on insulin action using 3T3-L1 adipocytes as a model system. RESEARCH DESIGN AND METHODS-A cross-sectional metabolic assessment of 21 patients with PCNT mutations was undertaken. Pericentrin expression in human tissues was profiled using quantitative real-time PCR. The effect of pericentrin knockdown on insulin action and adipogenesis in 3T3-L1 adipocytes was determined using Oil red 0 staining, gene-expression analysis, irnmunoblotting, and glucose uptake assays. Pericentrin expression and localization also was determined in skeletal muscle. RESULTS-Of 21 patients with genetic defects in PCNT, 18 had insulin resistance, which was severe in the majority of subjects. Ten subjects had confirmed diabetes (mean age of onset 15 years [range 5-28]), and 13 had metabolic dyslipidemia. All patients without insulin resistance were younger than 4 years old. Knockdown of pericentrin in adipocytes had no effect on proximal insulin signaling but produced a twofold impairment in insulin-stimulated glucose uptake, approximately commensurate with an associated defect in cell proliferation and adipogenesis. Pericentrin was highly expressed in human skeletal muscle, where it showed a perinuclear distribution. CONCLUSIONS-Severe insulin resistance and premature diabetes are common features of PCNT deficiency but are not congenital. Partial failure of adipocyte differentiation may contribute to this, but pericentrin deficiency does not impair proximal insulin action in adipocytes. Diabetes 60:925-935, 2011

  • 14.
    Jansson, Nina
    et al.
    Sahlgrenska Academy at University of Gothenburg, Perinatal Center, Institute of Neuroscience and Physiology, Göteborg, Sweden.
    Nisfelt, Anna
    Sahlgrenska Academy at University of Gothenburg, Perinatal Center, Institute of Neuroscience and Physiology, Göteborg, Sweden.
    Gellerstedt, Martin
    Department of Informatics, University West, Trollhättan, Sweden.
    Wennergren, Margareta
    Sahlgrenska Academy at University of Gothenburg, Department of Obstetrics and Gynecology, Göteborg, Sweden.
    Rossander-Hulthén, Lena
    Sahlgrenska Academy at University of Gothenburg, Department of Clinical Nutrition, Göteborg, Sweden.
    Powell, Theresa L.
    University of Cincinnati, Department of Obstetrics and Gynecology, Cincinnati, OH, United States.
    Jansson, Thomas
    Sahlgrenska Academy at University of Gothenburg, Perinatal Center, Institute of Neuroscience and Physiology, Göteborg, Sweden ; University of Cincinnati, Department of Obstetrics and Gynecology, Cincinnati, OH, United States.
    Maternal hormones linking maternal body mass index and dietary intake to birth weight2008Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 87, nr 6, s. 1743-1749Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Obese women often give birth to large-for-gestational age infants (typically defined as a birth weight greater than the 90th percentile), who are at risk of birth injuries and of developing metabolic syndrome later in life. The mechanisms underlying increased fetal growth remain to be established.

    Objective: We aimed to identify maternal hormones that can explain the link between dietary intake, body mass index (BMI), and birth weight.

    Design: Pregnant women with BMIs (in kg/m2) ranging from 17 to 44 (n = 49) were recruited in gestational weeks 8–12. Serum hormone concentrations were measured and dietary history interviews were performed in the first and third trimesters. Multiple regression models were produced to identify hormones that correlate with birth weight and are influenced by BMI or dietary factors.

    Results: We found a strong positive correlation between BMI and first- and third-trimester insulin and leptin concentrations and a negative correlation between BMI and first-trimester adiponectin and first- and third-trimester insulin-like growth factor binding protein-1 (IGFBP-1). Maternal total fat intake in the first trimester was positively correlated with maternal leptin and inversely correlated with adiponectin. In addition, third-trimester total fat intake was positively correlated with circulating resistin concentrations. First-trimester maternal serum resistin was positively correlated with birth weight, whereas third-trimester maternal IGFBP-1 was negatively correlated with birth weight.

    Conclusions: High first-trimester maternal serum resistin and low third-trimester IGFBP-1 were correlated with increased birth weight. We propose that low serum concentrations of IGFBP-1 represent a link between high BMI and increased fetal growth by increasing the bioavailability of insulin-like growth factor-I, which up-regulates placental nutrient transport.

  • 15.
    Johansson, Markus
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Sweden.
    Ulfenborg, Benjamin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Andersson, Christian X.
    Takara Bio Europe AB, Gothenburg, Sweden.
    Heydarkhan-Hagvall, Sepideh
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals, R&D AstraZeneca, Gothenburg, Sweden.
    Jeppsson, Anders
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Sweden / Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sartipy, Peter
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Late-stage Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Cardiac hypertrophy in a dish: a human stem cell based model2020Inngår i: Biology open, ISSN 2046-6390, Vol. 9, nr 9, artikkel-id bio052381Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96 h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

    Fulltekst (pdf)
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  • 16.
    Kokosar, Milana
    et al.
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Perfilyev, Alexander
    Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Scania University Hospital, Malmö, Sweden.
    Nilsson, Emma
    Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Scania University Hospital, Malmö, Sweden.
    Källman, Thomas
    Department of Medical Biochemistry and Microbiology, NBIS - National Bioinformatics Infrastructure Sweden, SciLifeLab, Uppsala University, Uppsala, Sweden.
    Ohlsson, Claes
    Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ling, Charlotte
    Epigenetics and Diabetes, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Clinical Research Centre, Scania University Hospital, Malmö, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden.
    A Single Bout of Electroacupuncture Remodels Epigenetic and Transcriptional Changes in Adipose Tissue in Polycystic Ovary Syndrome2018Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikkel-id 1878Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A single bout of electroacupuncture results in muscle contractions and increased whole body glucose uptake in women with polycystic ovary syndrome (PCOS). Women with PCOS have transcriptional and epigenetic alterations in the adipose tissue and we hypothesized that electroacupuncture induces epigenetic and transcriptional changes to restore metabolic alterations. Twenty-one women with PCOS received a single bout of electroacupuncture, which increased the whole body glucose uptake. In subcutaneous adipose tissue biopsies, we identified treatment-induced expression changes of 2369 genes (Q < 0.05) and DNA methylation changes of 7055 individual genes (Q = 0.11). The largest increase in expression was observed for FOSB (2405%), and the largest decrease for LOC100128899 (54%). The most enriched pathways included Acute phase response signaling and LXR/RXR activation. The DNA methylation changes ranged from 1-16%, and 407 methylation sites correlated with gene expression. Among genes known to be differentially expressed in PCOS, electroacupuncture reversed the expression of 80 genes, including PPAR gamma and ADIPOR2. Changes in the expression of Nr4 alpha 2 and Junb are reversed by adrenergic blockers in rats demonstrating that changes in gene expression, in part, is due to activation of the sympathetic nervous system. In conclusion, low-frequency electroacupuncture with muscle contractions remodels epigenetic and transcriptional changes that elicit metabolic improvement.

    Fulltekst (pdf)
    fulltext
  • 17.
    Kulkarni, Sameer S.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Håkan K. R.
    Karolinska Institutet, Stockholm, Sweden.
    Szekeres, Ferenc
    Karolinska Institutet, Stockholm, Sweden.
    Chibalin, Alexander V.
    Karolinska Institutet, Stockholm, Sweden.
    Krook, Anna
    Karolinska Institutet, Stockholm, Sweden.
    Zierath, Juleen R.
    Karolinska Institutet, Stockholm, Sweden.
    Suppression of 5 '-Nucleotidase Enzymes Promotes AMP-activated Protein Kinase (AMPK) Phosphorylation and Metabolism in Human and Mouse Skeletal Muscle2011Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, nr 40, s. 34567-34574Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The 5'-nucleotidase (NT5) family of enzyme dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. We hypothesized that gene silencing of NT5 enzymes to increase the intracellular availability of AMP would increase AMP-activated protein kinase (AMPK) activity and metabolism. We determined the role of cytosolic NT5 in metabolic responses linked to the development of insulin resistance in obesity and type 2 diabetes. Using siRNA to silence NT5C2 expression in cultured human myotubes, we observed a 2-fold increase in the AMP/ATP ratio, a 2.4-fold increase in AMPK phosphorylation (Thr(172)), and a 2.8-fold increase in acetyl-CoA carboxylase phosphorylation (Ser(79)) (p<0.05). siRNA silencing of NT5C2 expression increased palmitate oxidation by 2-fold in the absence and by 8-fold in the presence of 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside. This was paralleled by an increase in glucose transport and a decrease in glucose oxidation, incorporation into glycogen, and lactate release from NT5C2-depleted myotubes. Gene silencing of NT5C1A by shRNA injection and electroporation in mouse tibialis anterior muscle reduced protein content (60%; p<0.05) and increased phosphorylation of AMPK (60%; p<0.05) and acetyl-CoA carboxylase (50%; p<0.05) and glucose uptake (20%; p<0.05). Endogenous expression of NT5C enzymes inhibited basal lipid oxidation and glucose transport in skeletal muscle. Reduction of 5'-nucleotidase expression or activity may promote metabolic flexibility in type 2 diabetes.

  • 18.
    Maliqueo, Manuel
    et al.
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden / Laboratorio de Endocrinología y Metabolismo, Departamento de Medicina Occidente, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Rodrigues Marcondes, Rodrigo
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden / Laboratório de Ginecologia Estrutural e Molecular (LIM 58), Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Johansson, Julia
    Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Sun, Miao
    Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden / Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome2017Inngår i: Experimental Physiology, ISSN 0958-0670, E-ISSN 1469-445X, Vol. 102, nr 1, s. 113-127Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may improve its metabolic disturbances likely by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or -adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (β00 μg per day) or placebo pellets were implanted in pre-pubertal Wistar rats. Six weeks thereafter, rats were treated for 5–6 weeks with: low-frequency electroacupuncture (5 days per week), a -adrenergic blocker (propranolol hydrochloride, 0.1 mg kg-1) (5 days per week), or 17-estradiol (β.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue specific glucose uptake, lipid profile, adipocyte size, adiponectin and insulin serum concentrations, and gene expression in inguinal fat were measured. All treatments increased circulating levels of LDL-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusions, low-frequency electroacupuncture increased LDL-cholesterol without affecting the insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation probably mediated by estradiol action or -adrenergic pathway.

  • 19.
    Manti, Maria
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pironti, Gianluigi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    McCann Haworth, Sarah
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Zhengbing, Zhuge
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Carlström, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Daniel
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Heart and Vascular Theme, Heart Failure and Congenital Heart Disease Section, Karolinska University Hospital, Stockholm, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Maternal androgen excess induces cardiac hypertrophy and left ventricular dysfunction in female mice offspring2020Inngår i: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 116, nr 3, s. 619-632Artikkel i tidsskrift (Fagfellevurdert)
  • 20.
    Manti, Maria
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Qi, Xiaojuan
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Department of Physiology, Qiqihar Medical University, Qiqihar, China.
    Folmerz, Elin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lindén Hirschberg, Angelica
    Department of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.
    de Castro Barbosa, Thais
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Maliqueo, Manuel
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / West Division, Endocrinology and Metabolism Laboratory, School of Medicine, University of Chile, Santiago, Chile.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring2018Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 32, nr 8, s. 4158-4171Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

  • 21.
    Manti, Maria
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pui, Han-Pin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Edström, Sonja
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Risal, Sanjiv
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lindgren, Eva
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Ohlsson, Claes
    Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Jerlhag, Elisabet
    Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Deng, Qiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice2020Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 34, nr 11, s. 14440-14457Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nerve growth factor (NGF) is critical for the development and maintenance of the peripheral sympathetic neurons. NGF is also involved in the ovarian sympathetic innervation and in the development and maintenance of folliculogenesis. Women with the endocrine disorder, polycystic ovary syndrome (PCOS), have an increased sympathetic nerve activity and increased ovarian NGF levels. The role of ovarian NGF excess in the PCOS pathophysiology and in the PCOS-related features is unclear. Here, using transgenic mice overexpressesing NGF in the ovarian theca cells (17NF mice), we assessed the female embryonic development, and the reproductive and metabolic profile in adult females. Ovarian NGF excess caused growth restriction in the female fetuses, and a delayed gonocyte and primary oocyte maturation. In adulthood, the 17NF mice displayed irregular estrous cycles and altered ovarian expression of steroidogenic and epigenetic markers. They also exhibited an increased sympathetic output with increased circulating dopamine, and metabolic dysfunction reflected by aberrant adipose tissue morphology and function, impaired glucose metabolism, decreased energy expenditure, and hepatic steatosis. These findings indicate that ovarian NGF excess leads to adverse fetal development and to reproductive and metabolic complications in adulthood, mirroring common features of PCOS. This work provides evidence that NGF excess may be implicated in the PCOS pathophysiology. 

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  • 22.
    Mudry, Jonathan M.
    et al.
    Section for Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Massart, Julie
    Section for Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Szekeres, Ferenc L. M.
    Section for Integrative Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Krook, Anna
    Section for Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden / Section for Integrative Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle2015Inngår i: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 224, nr 3, s. 303-313Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    TWIST proteins are important for development of embryonic skeletal muscle and play a role in the metabolism of tumor and white adipose tissue. The impact of TWIST on metabolism in skeletal muscle is incompletely studied. Our aim was to assess the impact of TWIST1 and TWIST2 overexpression on glucose and lipid metabolism. In intact mouse muscle, overexpression of Twist reduced total glycogen content without altering glucose uptake. Expression of TWIST1 or TWIST2 reduced Pdk4 mRNA, while increasing mRNA levels of Il6, Tnf alpha, and Il1 beta. Phosphorylation of AKT was increased and protein abundance of acetyl CoA carboxylase ( ACC) was decreased in skeletal muscle overexpressing TWIST1 or TWIST2. Glycogen synthesis and fatty acid oxidation remained stable in C2C12 cells overexpressing TWIST1 or TWIST2. Finally, skeletal muscle mRNA levels remain unaltered in ob/ob mice, type 2 diabetic patients, or in healthy subjects before and after 3 months of exercise training. Collectively, our results indicate that TWIST1 and TWIST2 are expressed in skeletal muscle. Overexpression of these proteins impacts proteins in metabolic pathways and mRNA level of cytokines. However, skeletal muscle levels of TWIST transcripts are unaltered in metabolic diseases.

  • 23.
    Nilsson, Anne
    et al.
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Handlin, Linda
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Lidfors, Lena
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Petersson, Maria
    Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet, Stockholm, Sweden.
    Uvnäs-Moberg, Kerstin
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Interacting With a Visiting Dog Increases Fingertip Temperature in Elderly Residents of Nursing Homes2020Inngår i: Frontiers in Psychology, E-ISSN 1664-1078, Vol. 11, artikkel-id 01906Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to investigate whether interacting with a visiting dog influences fingertip temperature and cortisol levels in residents living in nursing homes for the elderly. The study included two groups, the dog group (n = 13) and the control group (n = 11–15) and lasted for 8 weeks for the dog group and 6 weeks for the control group. All participants were residents living at nursing homes for the elderly. The researchers visited small groups of the participants twice weekly during the entire study in both the dog and the control group. The visiting dog and the dog handler accompanied the researchers during weeks 3–6. Fingertip temperature was measured and saliva samples for cortisol determination were collected at 0, 20 and 60 min for the dog group and at 0 and 20 min for the control group. For analysis the study was divided into periods; Period 1 (week 1–2), Period 2 (week 3–4), Period 3 (week 5–6) and Period 4 (week 7–8, only the dog group). Mean values based on all data obtained at 0 and 20 min during period 1–3 were compared between groups. A second, separate analysis for the dog group also included data from 60 min and for period 4. For the dog group fingertip temperature increased significantly between period 1 and 2, 1 and 3 and 1 and 4 (p < 0.05). In addition, fingertip temperature rose significantly between 0 and 20 min and between 0 and 60 min within all periods. For the control group a significant decrease in fingertip temperature was observed between period 1 and 3 (p < 0.05). Fingertip temperature did not differ between the two groups during period 1, but was significantly higher for the dog group than for the control group during periods 2 and 3 (p < 0.05 and p < 0.001, respectively). Cortisol results are only presented descriptively due to that many samples had too low volume of saliva to be analyzed. In the present study interaction between elderly residents and a visiting dog resulted in increased fingertip temperature, probably reflecting a decrease in the activity of the sympathetic nervous system and therefore a decrease in stress levels.

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    fulltext
  • 24.
    Nilsson, Emma
    et al.
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kokosar, Milana
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Krook, Anna
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lindgren, Eva
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Källman, Thomas
    Department of Medical Biochemistry and Microbiology, National Bioinformatics Infrastructure Sweden, SciLifeLab, Uppsala University, Uppsala, Sweden.
    Martis, Mihaela M.
    National Bioinformatics Infrastructure Sweden, Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Højlund, Kurt
    Department of Endocrinology, Odense University, Odense C, Denmark.
    Ling, Charlotte
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome2018Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, nr 12, s. 4465-4477Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Context: Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective: To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants: In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index. matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results: Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of similar to 30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion: PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.

  • 25.
    Nilsson, Håkan
    Högskolan i Skövde, Institutionen för teknik och samhälle.
    Hjärnans signalsystem metodologi och funktion2007Inngår i: Neurodidaktik: Om hjärnvägar och knutpunkter / [ed] Aadu Ott & Carl E. Olivestam, Göteborg: Institutionen för pedagogik och didaktik, Neurodidaktiska kollegiet, Göteborgs universitet , 2007, s. 19-29Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 26.
    Olofsson, Peder S.
    et al.
    Center for Bioelectronic Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden / Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Steinberg, Benjamin E.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA / The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
    Sobbi, Roozbeh
    Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
    Cox, Maureen A.
    The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
    Ahmed, Mohamed N.
    Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Oswald, Michaela
    Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Szekeres, Ferenc
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Hanes, William M.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Introini, Andrea
    Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Liu, Shu Fang
    Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Holodick, Nichol E.
    Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Rothstein, Thomas L.
    Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Lövdahl, Cecilia
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Chavan, Sangeeta S.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Yang, Huan
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Pavlov, Valentin A.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Broliden, Kristina
    Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Andersson, Ulf
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Diamond, Betty
    The Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Miller, Edmund J.
    Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Arner, Anders
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Gregersen, Peter K.
    Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Backx, Peter H.
    Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada / Department of Biology, York University, Toronto, Ontario, Canada.
    Mak, Tak W.
    The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
    Tracey, Kevin J.
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Blood pressure regulation by CD4lymphocytes expressing choline acetyltransferase2016Inngår i: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 34, nr 10, s. 1066-1071Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4(+) T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals(1). Here we show that these CD4(+)CD44(hi)CD62L(Io) T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T-ChAT). Mice lacking ChAT expression in CD4(+) cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT(ChAT)) decreased blood pressure when infused into mice. Co-incubation of JT(ChAT) and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 T-ChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.

  • 27.
    Rehn, Therese
    et al.
    Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Uppsala, Sweden.
    Handlin, Linda
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Uvnäs-Moberg, Kerstin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Uppsala, Sweden.
    Keeling, Linda J.
    Swedish University of Agricultural Sciences, Department of Animal Environment and Health, Uppsala, Sweden.
    Dogs' endocrine and behavioural responses at reunion are affected by how the human initiates contact2014Inngår i: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 124, s. 45-53Artikkel i tidsskrift (Fagfellevurdert)
  • 28.
    Risal, Sanjiv
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Li, Congru
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden ; Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
    Luo, Qing
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Gustaw
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Ohlsson, Claes
    Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden ; Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lindgren, Eva
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Crisosto, Nicolas
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile ; Endocrinology Unit, Department of Medicine, Clínica Alemana de Santiago, Faculty of Medicine, Clinica Alemana, Universidad del Desarrollo, Santiago, Chile.
    Maliqueo, Manuel
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Echiburú, Barbara
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Chile.
    Recabarren, Sergio
    Laboratory of Animal Physiology and Endocrinology, Faculty of Veterinary Sciences, University of Concepción, Chillán, Chile.
    Petermann, Teresa Sir
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Chile.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Brusselaers, Nele
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden ; Global Health Institute, Antwerp University, Belgium.
    Qiao, Jie
    Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
    Deng, Qiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden ; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome2023Inngår i: Cell Reports Medicine, E-ISSN 2666-3791 , Vol. 4, nr 5, artikkel-id 101035Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The transgenerational maternal effects of polycystic ovary syndrome (PCOS) in female progeny are being revealed. As there is evidence that a male equivalent of PCOS may exists, we ask whether sons born to mothers with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a register-based cohort and a clinical case-control study, we find that PCOS-sons are more often obese and dyslipidemic. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in first-generation (F1) male offspring are passed down to F3. Sequencing of F1–F3 sperm reveals distinct differentially expressed (DE) small non-coding RNAs (sncRNAs) across generations in each lineage. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism, strengthening the translational relevance and highlighting a previously underappreciated risk of transmission of reproductive and metabolic dysfunction via the male germline. 

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  • 29.
    Risal, Sanjiv
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden / School of Medical Sciences, Örebro University, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Deng, Quiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Cesta, Carolyn E.
    Department of Medicine, Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mina A.
    School of Medical Sciences, Örebro University, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders2021Inngår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, nr 1, artikkel-id 45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring’s psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F3) in the androgenized lineage. In contrast, following the male germline, F3 male offspring (mF3) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F3 females in the androgenized lineage and eight genes in the obese lineage. In mF3 male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F1 and F2 offspring in the female germline did not develop anxiety-like behavior, while the F2 male offspring (mF2) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.

    Fulltekst (pdf)
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  • 30.
    Risal, Sanjiv
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pei, Yu
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pui, Han-Pin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Zhao, Zhiyi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Department of Gynecology, Shandong Provincial Qianfoshan Hospital, Jinan, China.
    Massart, Julie
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Ohlsson, Claes
    Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Lindgren, Eva
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Crisosto, Nicolas
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Carlos Schachtebeck 299, Santiago, Chile / Endocrinology Unit, Clinica Las Condes, Santiago, Chile.
    Maliqueo, Manuel
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Echiburú, Barbara
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Ladrón de Guevara, Amanda
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Sir-Petermann, Teresa
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden / School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rosenqvist, Mina A.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Cesta, Carolyn E.
    Department of Medicine, Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Deng, Qiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome2019Inngår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, nr 12, s. 1894-1904Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.

  • 31.
    Rune, A.
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Salehzadeh, F.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Szekeres, F.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Kuhn, I.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Osler, M. E.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Al-Khalili, L.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women2009Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 197, nr 3, s. 207-215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Methods: Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 +/- 2 years) and post-menopausal women (n = 10; 60 +/- 1 years). Results: mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 +/- 0.1 vs. 1.5 +/- 0.1-fold respectively) and incorporation into glycogen (2.3 +/- 0.3 vs. 2.0 +/- 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5'AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 +/- 0.6 vs. 2.0 +/- 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes. Conclusion: Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper.

  • 32.
    Samad, Manisha
    et al.
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ek, Joakim
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Börchers, Stina
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Krieger, Jean-Philippe
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden ; Institute of Veterinary Pharmacology and Toxicology, University of Zürich-VetSuisse, Zürich, Switzerland.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Skibicka, Karolina P.
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden ; Department of Nutritional Sciences, Pennsylvania State University, University Park, PA, United States ; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, United States.
    Asterholm, Ingrid Wernstedt
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model2024Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 14, nr 1, artikkel-id 563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects. 

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  • 33.
    Shrestha, Man Mohan
    et al.
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Wermelin, Sanne
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Asterholm, Ingrid W.
    Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Unit for Metabolic Physiology, Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Adiponectin Deficiency Alters Placenta Function but Does Not Affect Fetal Growth in Mice2022Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, nr 9, artikkel-id 4939Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adiponectin administration to pregnant mice decreases nutrient transport and fetal growth. An adiponectin deficiency, on the other hand, as seen in obese women during pregnancy, alters fetal growth; however, the mechanism is unclear. To determine the role of adiponectin on placenta function and fetal growth, we used adiponectin knockout, adiponectin heterozygote that displays reduced adiponectin levels, and wild-type mice on a control diet or high fat/high sucrose (HF/HS) diet. Triglycerides (TGs) in the serum, liver, and placenta were measured using colorimetric assays. Gene expression was measured using quantitative RT-PCR. Adiponectin levels did not affect fetal weight, but it reduced adiponectin levels, increased fetal serum and placenta TG content. Wildtype dams on a HF/HS diet protected the fetuses from fatty acid overload as judged by increased liver TGs in dams and normal serum and liver TG levels in fetuses, while low adiponectin was associated with increased fetal liver TGs. Low maternal adiponectin increased the expression of genes involved in fatty acid transport; Lpl and Cd36 in the placenta. Adiponectin deficiency does not affect fetal growth but induces placental dysfunction and increases fetal TG load, which is enhanced with obesity. This could lead to imprinting effects on the fetus and the development of metabolic dysfunction in the offspring. 

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  • 34.
    Stener-Victorin, Elisabet
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Department of Physiology, Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Maliqueo, Manuel
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Endocrinology and Metabolism Laboratory, West division, School of Medicine, University of Chile, Santiago, Chile.
    Acupuncture2018Inngår i: Infertility in Women with Polycystic Ovary Syndrome: Pathogenesis and Management / [ed] Stefano Palomba, Springer, 2018, s. 227-245Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Acupuncture involving insertion of thin sterile needles into the skin, muscles, and fibrous/fat tissues is a part of traditional Chinese medicine (TCM). Western medical acupuncture described in this chapter is an adaptation of Chinese acupuncture using current knowledge of anatomy, physiology, pathology, and evidence-based medicine, instead of using concepts such as meridiansyin/yang, and circulation of qi. This chapter describes the use of acupuncture in the treatment of women with polycystic ovary syndrome (PCOS) from a western medical approach including potential mechanism of action, experimental data as well as clinical data.

  • 35.
    Stener-Victorin, Elisabet
    et al.
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Eriksson, Gustaw
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Shrestha, Man Mohan
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Rodriguez Paris, Valentina
    School of Biomedical Sciences, University of New South Wales, Sydney, Australia.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Banks, Jasmine
    School of Biomedical Sciences, University of New South Wales, Sydney, Australia ; Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, NSW, Australia.
    Samad, Manisha
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Perian, Charlène
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Jude, Baptiste
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Engman, Viktor
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Boi, Roberto
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Nilsson, Emma
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden.
    Ling, Charlotte
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden.
    Nyström, Jenny
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Wernstedt Asterholm, Ingrid
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Turner, Nigel
    School of Biomedical Sciences, University of New South Wales, Sydney, Australia ; Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, NSW, Australia.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Proteomic analysis shows decreased Type I fibers and ectopic fat accumulation in skeletal muscle from women with PCOS2024Inngår i: eLife, ISSN 2050-084X, Vol. 12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Polycystic ovary syndrome’s (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead tochanges in protein levels and biological function. Methods: To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Results: Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differences in protein activity and function. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Conclusions: Our results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids and fewer oxidative insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective.

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  • 36.
    Stener-Victorin, Elisabet
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
    Risal, Sanjiv
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Origins and Impact of Psychological Traits in Polycystic Ovary Syndrome2019Inngår i: Medical sciences, ISSN 2076-3271, Vol. 7, nr 8, artikkel-id 86Artikkel, forskningsoversikt (Fagfellevurdert)
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  • 37.
    Stener-Victorin, Elisabet
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Padmanabhan, Vasantha
    Departments of Pediatrics, Obstetrics and Gynecology, and Environmental Health Sciences, University of Michigan, Ann Arbor, USA.
    Walters, Kirsty A.
    Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
    Campbell, Rebecca E.
    Centre for Neuroendocrinology and Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Giacobini, Paolo
    University of Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, France.
    Dumesic, Daniel A.
    Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, USA.
    Abbott, David H.
    Department of Obstetrics and Gynecology, Wisconsin National Primate Research Center, University of Wisconsin, Madison, USA.
    Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome2020Inngår i: Endocrine reviews, ISSN 0163-769X, E-ISSN 1945-7189, Vol. 41, nr 4, artikkel-id bnaa010Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, PCOS and its accompanying morbidities are likely underdiagnosed, averaging > 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females. 

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  • 38.
    Synnergren, Jane
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Améen, Caroline
    Cellartis, Gothenburg, Sweden.
    Lindahl, Anders
    Dept of Clinical Chemistry/Transfusion Medicine, Sahlgrenska University Hospital, Sweden.
    Olsson, Björn
    Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Sartipy, Peter
    Cellartis, Gothenburg, Sweden .
    Expression of microRNAs and their target mRNAs in human stem cell-derived cardiomyocyte clusters and in heart tissue2011Inngår i: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, nr 10, s. 581-594Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent studies have shown that microRNAs (miRNAs) act as posttranscriptional regulators and that they play important roles during heart development and in cardiac function. Thus, they may provide new means of altering stem cell fate and differentiation processes. However, information about the correlation between global miRNA and mRNA expression in cardiomyocyte clusters (CMCs) derived from human embryonic stem cells (hESC) and in fetal and adult heart tissue is lacking. In the present study the global miRNA and mRNA expression in hESC-derived CMCs and in fetal and adult heart tissue was investigated in parallel using microarrays. Target genes for the differentially expressed miRNAs were predicted using computational methods, and the concordance in miRNA expression and mRNA levels of potential target genes was determined across the experimental samples. The biology of the predicted target genes was further explored regarding their molecular functions and involvement in known regulatory pathways. A clear correlation between the global miRNA expression and corresponding target mRNA expression was observed. Using three different sources of cardiac tissue-like samples, we defined the similarities between in vitro hESC-derived CMCs and their in vivo counterparts. The results are in line with previously reported observations that miRNAs repress mRNA expression and additionally identify a number of novel miRNAs with potential important roles in human cardiac tissue. The concordant miRNA expression pattern observed among all the cardiac tissue-like samples analyzed here provide a starting point for future ambitious studies aiming towards assessment of the functional roles of specific miRNAs during cardiomyocyte differentiation.

  • 39.
    Szekeres, Ferenc
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Chadt, Alexandra
    German Institute of Human Nutrition, Potsdam-Rehbruecke, Department of Pharmacology, Nuthetal, Germany.
    Tom, Robby Z.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Deshmukh, Atul S.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Chibalin, Alexander V.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Björnholm, Marie
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Al-Hasani, Hadi
    German Institute of Human Nutrition, Potsdam-Rehbruecke, Department of Pharmacology, Nuthetal, Germany.
    Zierath, Juleen R.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden / Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism2012Inngår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 303, nr 4, s. E524-E533Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Szekeres F, Chadt A, Tom RZ, Deshmukh AS, Chibalin AV, Bjornholm M, Al-Hasani H, Zierath JR. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism. Am J Physiol Endocrinol Metab 303: E524-E533, 2012. First published June 12, 2012; doi:10.1152/ajpendo.00605.2011.-The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose and insulin tolerance tests were normal in TBC1D1-deficient Nob1.10(SJL) mice, yet the 4-h-fasted insulin concentration was increased. Insulin-stimulated peripheral glucose utilization during a euglycemic hyperinsulinemic clamp was similar between genotypes, whereas the suppression of hepatic glucose production was increased in TBC1D1-deficient mice. In isolated extensor digitorum longus (EDL) but not soleus muscle, glucose transport in response to insulin, AICAR, or contraction was impaired by TBC1D1 deficiency. The reduction in glucose transport in EDL muscle from TBC1D1-deficient Nob1.10(SJL) mice may be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice. In conclusion, TBC1D1 plays a role in regulation of glucose metabolism in skeletal muscle. Moreover, functional TBC1D1 is required for AICAR- or contraction-induced metabolic responses, implicating a role in energy-sensing signals.

  • 40.
    Szekeres, Ferenc L. M.
    et al.
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Division of Genetic Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Walum, Erik
    Glucox Biotech AB, Färentuna, Sweden.
    Wikström, Per
    Glucox Biotech AB, Färentuna, Sweden.
    Arner, Anders
    Division of Genetic Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockhom, Sweden ; Department of Clinical Sciences Lund, Thoracic Surgery, Lund University, c/o Igelösa Life Science AB, Lund, Sweden.
    A small molecule inhibitor of Nox2 and Nox4 improves contractile function after ischemia–reperfusion in the mouse heart2021Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikkel-id 11970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The NADPH oxidase enzymes Nox2 and 4, are important generators of Reactive oxygen species (ROS). These enzymes are abundantly expressed in cardiomyocytes and have been implicated in ischemia–reperfusion injury. Previous attempts with full inhibition of their activity using genetically modified animals have shown variable results, suggesting that a selective and graded inhibition could be a more relevant approach. We have, using chemical library screening, identified a new compound (GLX481304) which inhibits Nox 2 and 4 (with IC50 values of 1.25 µM) without general antioxidant effects or inhibitory effects on Nox 1. The compound inhibits ROS production in isolated mouse cardiomyocytes and improves cardiomyocyte contractility and contraction of whole retrogradely (Langendorff) perfused hearts after a global ischemia period. We conclude that a pharmacological and partial inhibition of ROS production by inhibition of Nox 2 and 4 is beneficial for recovery after ischemia reperfusion and might be a promising venue for treatment of ischemic injury to the heart. 

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  • 41.
    Szekeres, Ferenc
    et al.
    Karolinska Institutet, Department of physiology and pharmacology, Division of genetic physiology, Stockholm, Sweden.
    Walum, Erik
    Glucox Biotech AB, Stockholm, Sweden.
    Wikström, P.
    Glucox Biotech AB, Stockholm, Sweden.
    Arner, A.
    Karolinska Institutet, Department of physiology and pharmacology, Division of genetic physiology, Stockholm, Sweden.
    A small molecule inhibitor of Nox2 and Nox4 improves cardiac contractility after ischemia-reperfusion in the mouse heart2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, nr s696, s. 93-93Artikkel i tidsskrift (Fagfellevurdert)
  • 42.
    Uvnäs-Moberg, Kerstin
    et al.
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Handlin, Linda
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande.
    Kendall-Tackett, Kathleen
    Texas Tech University School of Medicine, Amarillo, TX, USA.
    Petersson, Maria
    Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet, Sweden.
    Oxytocin is a principal hormone that exerts part of its effects by active fragments2019Inngår i: Medical Hypotheses, ISSN 0306-9877, E-ISSN 1532-2777, Vol. 133, s. 1-9, artikkel-id 109394Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Oxytocin is a nonapeptide consisting of a cyclic six amino-acid structure and a tail of three amino acids. It was originally known for its ability to induce milk ejection and to stimulate uterine contractions. More recently, oxytocin has been shown to stimulate social behaviors, and exert pain-relieving, anti-stress/anti-inflammatory and restorative effects. We hypothesize that oxytocin is a principal hormone that, in part, exerts its effects after degradation to active fragments with more specific effect profiles. Experimental findings on rats show that administered oxytocin exerts biphasic effects. For example, after an initial increase in pain threshold, a second more long-lasting increase follows. Blood pressure and cortisol levels initially increase and then reverse into a long-lasting decrease in blood pressure and cortisol. Whereas the initial effects are, the second-phase effects are not blocked by an oxytocin antagonist, but by an opioid mu-antagonist and by an alpha 2-adrenoreceptor antagonist, respectively, suggesting that other receptors are involved. Repeated administration of oxytocin induces multiple anti-stress effects, which are mediated by alpha 2-adrenoreceptors. Repeated administration of linear oxytocin and linear oxytocin fragments with a retained C-terminal reduce spontaneous motor activity, a sedative or anti-stress effect, suggesting that alpha 2-adrenoreceptors have been activated. In contrast, linear mid-fragments stimulate motor activity. Low-intensity stimulation of cutaneous nerves in rats, as well as breastfeeding and skin-to-skin contact between mothers and babies, trigger immediate anti-stress effects. Some of these effects are likely caused by open ring/linear C-terminal fragments activating alpha 2-adrenoreceptors. Oxytocin fragments may be pre-formed and released in the brain or created by metabolic conversion of the principal hormone oxytocin in the central nervous system. Oxytocin and its fragments may also be released from peripheral sites, such as peripheral nerves, the gastrointestinal tract, and blood vessels in response to decreased sympathetic or increased parasympathetic nervous tone. Smaller fragments of oxytocin produced in the periphery may easily pass the blood-brain barrier to induce effects in the brain. In conclusion, oxytocin is linked to many different, sometimes opposite effects. The intact cyclic molecule may act to initiate social interaction and associated psychophysiological effects, whereas linear oxytocin and C-terminal fragments may induce relaxation and anti-stress effects following social interaction. In this way, the principal hormone oxytocin and its fragments may take part in a behavioral sequence, ranging from approach and interaction to calm and relaxation. Linear fragments, with an exposed cysteine-residue, may exert anti-inflammatory and antioxidant effects and thereby contribute to the health-promoting effects of oxytocin. 

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  • 43.
    Uvnäs-Moberg, Kerstin
    et al.
    Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.
    Handlin, Linda
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Petersson, Maria
    Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet, Sweden.
    Neuroendocrine mechanisms involved in the physiological effects caused by skin-to-skin contact - With a particular focus on the oxytocinergic system2020Inngår i: Infant Behavior and Development, ISSN 0163-6383, E-ISSN 1879-0453, Vol. 61, nr November, artikkel-id 101482Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The positive clinical effects caused by skin-to-skin contact immediately after birth or after repeated skin-to-skin contact of premature infants (kangaroo care) or fullterm infants are well documented in the literature. However, information regarding the physiological mechanisms mediating these effects are surprisingly scarce and incomplete. In this article the oxytocinergic system and the cutaneous sensory pathways by which the oxytocinergic system is activated in response to skin-to-skin contact are presented in more detail. In addition, we discuss how the effects of skin-to-skin treatment can be attributed to different aspects of the effect spectrum of the oxytocinergic or calm and connection system.

    The structure of the oxytocinergic system, comprising the peripheral (circulating, hormonal) and the central (neurotransmitter) components, as well as, the pathways and mechanisms by which these functions are coordinated are described. Also the various effects induced by the oxytocinergic system (the calm and connection system) are reviewed.

    The sensory pathways, which include visual, auditory, olfactory and tactile stimuli, given and received by both mother and newborn and which activate the oxytocinergic system in response to skin-to-skin contact, are reviewed. A special emphasis is placed on the role of cutaneous sensory nerves and their activation by touch, light pressure and in particular warmth. The important role of the rise and the pulsatility of maternal temperature in mediating the positive effects of skin-to-skin contact in the newborn is highlighted. The concept of maternal giving of warmth and its possible link to the experience of trust and safety in the newborn is discussed from an evolutionary perspective.

    The effects induced by skin-to-skin contact can be attributed to the different functions of the oxytocinergic system. Ameliorated social interaction (e.g., more tactile and auditory interaction, more sensitive and synchronous interaction between mother and baby, the baby’s crawling behavior) are expressions of oxytocin’s ability to stimulate social interaction. The decreased levels of fear and stress are expressions of oxytocin’s ability to reduce the activity of the amygdala and of the stress system, e.g. the activity in the HPA-axis and the sympathetic nervous system. Increased HRV, increased activity in endocrine system of the gastrointestinal tract as well as stimulation of growth and maturation are examples of oxytocin’s ability to stimulate the activity of the parasympathetic nervous system and other peripheral and central mechanisms related to restoration and growth.

    The propensity of different types of treatment with skin-to-skin contact to induce long-term effects is also highlighted. We propose that the sustained effects caused by skin-to-skin contact are induced by an enduring shift in the balance between the oxytocinergic system (the calm and connection system) and the stress system (fight flight reaction) in favor of the oxytocinergic system. This shift leads to a sustained decrease in the HPA-axis and the sympathetic nervous system probably involving alpha 2-adrenoceptors.

    It is of clinical importance to be aware of the mechanisms by which skin-to-skin contact induces short and longterm positive effects in parents and newborns. If ward routines are adapted to ascertain a maximal stimulation of these mechanisms, the function of the oxytocinergic system will be optimized, which will be linked to a better clinical outcome for parents and newborns.

  • 44.
    Warrén-Stomberg, Margareta
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Lorentzen, Per
    Skaraborgs Hospital, Skövde, Sweden.
    Joelsson, Håkan
    Skaraborgs Hospital, Skövde, Sweden.
    Lindquist, Helene
    Skaraborgs Hospital, Skövde, Sweden.
    Haljamäe, Hengo
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Postoperative pain management on surgical wards: impact of database documentation of anesthesia organized services2003Inngår i: Pain Management Nursing, ISSN 1524-9042, E-ISSN 1532-8635, Vol. 4, nr 4, s. 155-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Postoperative pain management (POPM) should be based on an organization exploiting existing expertise and documenting the outcome of the POPM in each individual patient. The aims of the present study were to evaluate the adequacy of database documentation of POPM of an anesthesia organized, nurse-based, anesthesiologist-supervised acute pain service (APS) on surgical wards and to assess to what extent the information obtained was continuously used to improve practice. From 2890 registered cases in the database (patient controlled analgesia, n = 1975; epidural analgesia [EDA], n = 915), a homogeneous two-year sample of documentation charts from use of EDA for POPM in connection with major, open, abdominal surgical procedures (n = 381) was chosen for detailed analysis. The data charts contained information on patient data, drug dosage, total amount of infused drug, duration of EDA treatment, occurrence of side effects, and patient’s level of satisfaction. The database information was easily accessible making assessment of relevant aspects of the routines, including associations between analgesic technique, patient related factors, and satisfaction with the services, immediately available. Only 58% of the data charts were properly completed and fed into the database but the clinical safety of the missing nondatabase documented sample was not found jeopardized. Although the database documentation routines were considered to fulfill basic requirements of data collection and monitoring of the appropriateness of POPM, they were not found to function optimally. The reason seemed to be inadequate feedback of information between the parties involved in the POPM services. The present study stresses the importance of establishing routines for adequate, continuous feedback of recorded audit data from the APS team to the surgical wards for the maintenance of a high level of compliance with accepted guidelines.

  • 45.
    Warrén-Stomberg, Margareta
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Sjöström, Björn
    Högskolan i Skövde, Institutionen för vård och natur.
    Haljamae, Hengo
    Routine intra-operative assessment of pain and/or depth of anaesthesia by nurse anaesthetists in clinical practice2001Inngår i: Journal of Clinical Nursing, ISSN 1365-2702, Vol. 19, nr 4, s. 429-436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    • Patient safety and comfort during general anaesthesia and surgery are to a considerable extent dependent on the capability of anaesthesia personnel to interpret directly monitored as well as indirect clinical signs of pain and/or depth of anaesthesia.

    • The aim of the present study was to evaluate how nurse anaesthetists in their clinical routine work assess and interpret intra-operative responses evoked by pain stimuli and/or insufficient depth of anaesthesia.

    • A questionnaire was designed to assess the perceived relevance and validity of cardiovascular, respiratory, mucocutaneous, eye-associated, and muscular responses for routine assessment of intra-operative pain and/or insufficient depth of anaesthesia in patients undergoing surgery under general anaesthesia.

    • Data were obtained from 223 nurse anaesthetists working at nine different university anaesthesia departments in Sweden.

    • A number of significant indicators for pain and depth of anaesthesia could be identified for spontaneously breathing as well as for mechanically ventilated patients. No variable was considered entirely specific for either intra-operative pain or depth of anaesthesia. Changes in breathing rate/volume, central haemodynamics (BP, HR), lacrimation, and presence of moist and sticky skin were given higher score values as indicators of pain than as indicators of depth of anaesthesia. Occurrence of grimaces, attempted movements, and presence of non-centred pupils were variables considered more indicative of insufficient depth of anaesthesia than intra-operative pain.

    • In conclusion, it is obvious from the present data that indirect physiological signs of intra-operative pain and depth of anaesthesia are still considered of importance by Swedish anaesthesia nurses in the anaesthetic management of surgical patients.

  • 46.
    Warrén-Stomberg, Margareta
    et al.
    Högskolan i Skövde, Institutionen för hälso- och vårdvetenskap.
    Sjöström, Björn
    Högskolan i Skövde, Institutionen för hälso- och vårdvetenskap. Göteborg University.
    Haljamäe, Hengo
    Sahlgrenska University Hospital, Göteborg.
    Assessing Pain Responses During General Anesthesia2001Inngår i: AANA Journal, ISSN 0094-6354, Vol. 69, nr 3, s. 218-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Major technical and pharmacological achievements in recent years have greatly influenced the practice of anesthesia. Clinical signs related to the main aspects of anesthesia, i.e., hypnosis, analgesia, and muscular relaxation, are increasingly obtainable from variables supplied by the monitoring equipment. It is not known, however, to what extent more indirect, patient-associated clinical signs of pain/depth of anesthesia are still considered of importance and relied on in the intraoperative management of surgical patients. The aims of the present study were to assess what clinical signs, indirect as well as monitor-derived, are considered indicative of intraoperative pain or depth of anesthesia by nurse anesthetists during general anesthesia. In connection with anesthetic management of surgical patients, Swedish nurse anesthetists (N = 40) were interviewed about clinical signs that they routinely assessed and were asked if the observed signs were considered indicative mainly of intraoperative pain or depth of anesthesia. It was found that skin-associated responses (temperature, color, moisture/stickiness) were commonly considered to indicate intraoperative pain rather than depth of anesthesia. Respiratory movements, eye reactions, and circulatory responses were considered to be indicative of either pain or insufficient depth of anesthesia. The present data indicate that indirect physiological signs are still considered of major importance by anesthesia nurses during the anesthetic management of surgical patients.

  • 47.
    Warrén-Stomberg, Margareta
    et al.
    Högskolan i Skövde, Institutionen för vård och natur. University of Göteborg.
    Sjöström, Björn
    Högskolan i Skövde, Institutionen för vård och natur.
    Haljamäe, Hengo
    Sahlgrenska University Hosptial, University of Göteborg.
    The role of the nurse anesthetist in the planning of postoperative pain management2003Inngår i: AANA Journal, ISSN 0094-6354, Vol. 71, nr 3, s. 197-202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adequate pain relief after surgery is essential for avoiding pain-associated stress and patient comfort in the postoperative period. The Swedish nurse anesthetist has an important role in the intraoperative management of the surgical patient by assessing and moderating individual physiological response evoked by surgical stimuli during general anesthesia. The extent to which knowledge of specific individual response patterns are used to plan postoperative pain management is unknown. The aim of the present study was to assess the role of the nurse anesthetist in planning early postoperative pain management for surgical patients. Nurse anesthetists (N = 101) at 4 academic hospitals in Sweden responded to a questionnaire focusing, in addition to demographic data, on intraoperative routines for postoperative pain management, perceived clinical relevance of used routines, personal involvement (in addition to existing routines) in postoperative pain management, factors influencing pain alleviation requirements, and the potential role of the nurse anesthetist for improved postoperative pain management. We found that type of anesthesia and type of surgical procedure were both factors considered important for postoperative pain management. A majority of the participants believed that pain management approaches were not appropriately individualized to the patient.

  • 48.
    Warrén-Stomberg, Margareta
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Wickström, Kerstin
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Joelsson, Håkan
    Högskolan i Skövde, Institutionen för vård och natur. Skaraborgs Hospital, Skövde, Sweden.
    Sjöström, Björn
    Högskolan i Skövde, Institutionen för vård och natur. Sahlgrenska University Hospital, Göteborg, Sweden.
    Haljamäe, Hengo
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Postoperative pain management on surgical wards: do quality assurance strategies result in long-term effects on staff member attitudes and clinical outcomes?2003Inngår i: Pain Management Nursing, ISSN 1524-9042, E-ISSN 1532-8635, Vol. 4, nr 1, s. 11-22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Postoperative pain management (POPM) remains suboptimal on surgical wards in many countries despite the availability of effective analgesics, new technologies for drug administration, and clinical practice guidelines for pain management. The aim of the present study was to assess remaining long-term effects on pain management routines, patient experiences, and staff member attitudes in surgical wards more than 3 years after introduction of a quality assurance program for POPM and compare the findings to those of an organization where a corresponding systematic, entire hospital, quality assurance program had not been completed. A descriptive and comparative design, based on survey data from both patients (N = 110) and staff members (N = 51) on urologic surgery wards, was used. Significant (p < .05 to p < .0002) overall relationships were observed for identified shortages in pain management routines (lack of preoperative information, inadequate preoperative discussions on pain management, wait for pain killer) and reported experience of pain, nausea, or vomiting in the postoperative period. The quality assurance program, anesthesia-based pain services using a nurse-based anesthesiologist-supervised model, resulted in more adequate pain management routines, better patient satisfaction with POPM, and increased confidence in pain management among nurses on the surgical wards. On the basis of the present study it may be concluded that more than 3 years after the introduction of a quality assurance program for POPM in surgical wards, the pain management routines, patient experiences, and staff member attitudes have remained markedly improved and in accordance with the aims of accepted clinical practice guidelines for surgical pain management.

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