Högskolan i Skövde

his.sePublikasjoner
Endre søk
Begrens søket
1 - 27 of 27
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • apa-cv
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 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. 

    Fulltekst (pdf)
    fulltext
  • 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. 

    Fulltekst (pdf)
    fulltext
  • 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.

    Fulltekst (pdf)
    fulltext
  • 6.
    Davegårdh, Cajsa
    et al.
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    Säll, Johanna
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, 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.
    Broholm, Christa
    Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
    Volkov, Petr
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    Perfilyev, Alexander
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    Henriksen, Tora Ida
    The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark.
    Wu, Yanling
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Hjort, Line
    Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark ; Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
    Brøns, Charlotte
    Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
    Hansson, Ola
    Genomics, Diabetes and Endocrinology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden ; Finnish Institute of Molecular Medicine, University of Helsinki, Finland.
    Pedersen, Maria
    The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark.
    Würthner, Jens U.
    ADC Therapeutics, Biopole, Epalinges, Switzerland.
    Pfeffer, Klaus
    Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Germany.
    Nilsson, Emma
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    Vaag, Allan
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pircs, Karolina
    Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Sweden.
    Scheele, Camilla
    The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
    Ling, Charlotte
    Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
    VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics2021Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 12, nr 1, artikkel-id 2431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39+/− mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. 

    Fulltekst (pdf)
    fulltext
  • 7.
    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.

    Fulltekst (pdf)
    fulltext
  • 8.
    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.

  • 9.
    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
  • 10.
    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.

  • 11.
    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)
  • 12.
    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.

  • 13.
    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. 

    Fulltekst (pdf)
    fulltext
  • 14.
    Manti, Maria
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Skeletal Muscle Immunometabolism in Women With Polycystic Ovary Syndrome: A Meta-Analysis2020Inngår i: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 11, artikkel-id 573505Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting up to 15% of women at reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including hyperinsulinemia and insulin resistance and a 4-fold increased risk of developing type 2 diabetes. Despite the high prevalence the pathophysiology of the syndrome is unclear. Insulin resistance in women with PCOS likely affect the skeletal muscle and recently it was demonstrated that changes in DNA methylation affects the gene expression in skeletal muscle that in part can explain their metabolic abnormalities. The objective of this work was to combine gene expression array data from different datasets to improve statistical power and thereby identify novel biomarkers that can be further explored. In this narrative review, we performed a meta-analysis of skeletal muscle arrays available from Gene Expression Omnibus and from publications. The eligibility criteria were published articles in English, and baseline (no treatment) skeletal muscle samples from women with PCOS and controls. The R package Metafor was used for integration of the datasets. One hundred and fourteen unique transcripts were differentially expressed in skeletal muscle from women with PCOS vs. controls (q < 0.05), 87% of these transcripts have not been previously identified as altered in PCOS muscle. ING2, CDKAL1, and AKTIP had the largest differential increase in expression, and TSHZ2, FKBP2, and OCEL1 had the largest decrease in expression. Two genes, IRX3 and CDKAL1 were consistently upregulated (q < 0.05) in the individual analyses and meta-analysis. Based on the meta-analysis, we identified several dysregulated immunometabolic pathways as a part of the molecular mechanisms of insulin resistance in the skeletal muscle of women with PCOS. The transcriptomic data need to be verified by functional analyses as well as proteomics to advance our understanding of PCOS specific insulin resistance in skeletal muscle.

    Fulltekst (pdf)
    fulltext
  • 15.
    Marcondes, Rodrigo R.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Disciplina de Ginecologia, Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    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.
    Fornes, Romina
    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, Gothenburg, Sweden.
    Hu, Min
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ivarsson, Niklas
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Carlström, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Cushman, Samuel W.
    Experimental Diabetes, Metabolism, and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
    Stenkula, Karin G.
    Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
    Maciel, Gustavo A. R.
    Disciplina de Ginecologia, Laboratorio de Ginecologia Estrutural e Molecular (LIM 58), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Exercise differentially affects metabolic functions and white adipose tissue in female letrozole-and dihydrotestosterone-induced mouse models of polycystic ovary syndrome2017Inngår i: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 448, s. 66-76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. 

  • 16.
    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.

  • 17.
    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. 

    Fulltekst (pdf)
    fulltext
  • 18.
    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)
    fulltext
  • 19.
    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.

  • 20.
    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. 

    Fulltekst (pdf)
    fulltext
  • 21.
    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. 

    Fulltekst (pdf)
    fulltext
  • 22.
    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.

  • 23.
    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.

    Fulltekst (pdf)
    fulltext
  • 24.
    Stener-Victorin, Elisabet
    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, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Soligo, M.
    Institute of Translational Pharmacology – CNR, Rome, Italy.
    Protto, V.
    Institute of Translational Pharmacology – CNR, Rome, Italy.
    Manni, L.
    Institute of Translational Pharmacology – CNR, Rome, Italy.
    Jerlhag, E.
    Institute of Neuroscience and Physiology, Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kokosar, M.
    Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Sazonova, A.
    Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Behre, C. J.
    Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lind, M.
    Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Ohlsson, C.
    Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Højlund, K.
    Department of Endocrinology, Odense University Hospital, Odense, Denmark.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy University, of Gothenburg, Gothenburg, Sweden.
    Changes in HbA 1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture2016Inngår i: Obesity Science and Practice, ISSN 2055-2238, Vol. 2, nr 4, s. 426-435Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim

    Insulin sensitivity is ~40% lower in women with polycystic ovary syndrome (PCOS) than in controls. We tested the hypothesis that 5weeks of electroacupuncture treatment improves glucose regulation and androgen levels in overweight/obese women with PCOS.

    Material and Methods

    Seventeen women with PCOS, aged 18 to 38years, with a body mass index (BMI) ≥25 kg/m2 and diagnosed with PCOS were included in this experimental and feasibility study and subjected to five weeks of electroacupuncture treatments three times/week. The primary outcome was changes in whole‐body glucose homeostasis measured by euglycemic hyperinsulinemic clamp before and after the intervention. Secondary outcome were changes in HbA1c, circulating catecholamines, adipocyte size and adipose tissue expression of sex steroids and nerve growth factor (NGF).

    Results

    No significant change in glucose homeostasis was observed, but HbA1c decreased by 9.5% (p=0.004), circulating testosterone decreased by 22% (p=0.0007) and dihydrotestosterone decreased by 12% (p=0.007). The two vagal activity markers of plasma serotonin levels and the dopamine metabolite homovanillic acid decreased by 21% (p=0.027) and 20% (p=0.011), respectively. Adipose tissue concentrations of testosterone decreased by 18% (p=0.049), and androstenedione decreased by 13% (p=0.035), and mature NGF/proNGF ratio, a marker of sympathetic activity, increased (p=0.04). These changes occurred without changes in anthropometrics.

    Conclusion

    Five weeks of electroacupuncture treatment improves HbA1c and circulating and adipose tissue androgens in women with PCOS. This effect is mediated, at least in part, via modulation of vagal activity and adipose tissue sympathetic activity. Based on these findings, we have recently initiated a randomized controlled study (NTC02647827).

    Fulltekst (pdf)
    fulltext
  • 25.
    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)
    Fulltekst (pdf)
    fulltext
  • 26.
    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. 

    Fulltekst (pdf)
    fulltext
  • 27.
    Wu, Yanling
    et al.
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Chanclón, Belén
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Micallef, Peter
    Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Stener-Victorin, Elisabet
    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, 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.
    Maternal adiponectin prevents visceral adiposity and adipocyte hypertrophy in prenatal androgenized female mice2021Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 35, nr 4, artikkel-id e21299Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hyperandrogenism is the main characteristic of polycystic ovary syndrome, which affects placental function and fetal growth, and leads to reproductive and metabolic dysfunction in female offspring. Adiponectin acts on the placenta and may exert endocrine effects on the developing fetus. This study aims to investigate if maternal and/or fetal adiponectin can prevent metabolic and reproductive dysfunction in prenatal androgenized (PNA) female offspring. Adiponectin transgenic (APNtg) and wild-type dams received dihydrotestosterone/vehicle injections between gestational days 16.5-18.5 to induce PNA offspring, which were followed for 4 months. Offspring from APNtg dams were smaller than offspring from wild-type dams, independent of genotype. Insulin sensitivity was higher in wild-type mice from APNtg dams compared to wild-types from wild-type dams, and insulin sensitivity correlated with fat mass and adipocyte size. PNA increased visceral fat% and adipocyte size in wild-type offspring from wild-type dams, while wild-type and APNtg offspring from APNtg dams were protected against this effect. APNtg mice had smaller adipocytes than wild-types and this morphology was associated with an increased expression of genes regulating adipogenesis (Ppard, Pparg, Cebpa, and Cebpb) and metabolism (Chrebp and Lpl). Anogenital distance was increased in all PNA-exposed wild-type offspring, but there was no increase in PNA APNtg offspring, suggesting that adiponectin overexpression protects against this effect. In conclusion, elevated adiponectin levels in utero improve insulin sensitivity, reduce body weight and fat mass gain in the adult offspring and protect against PNA-induced visceral adiposity. In conclusion, these data suggest that PNA offspring benefit from prenatal adiponectin supplementation. 

    Fulltekst (pdf)
    fulltext
1 - 27 of 27
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • apa-cv
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf