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  • 1.
    Benrick, Anna
    et al.
    University of Skövde, School of Health Sciences. University of Skövde, Digital Health Research (DHEAR). 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 syndrome2020In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 105, no 6, p. 2027-2041Article in journal (Refereed)
    Abstract [en]

    Context

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

    Objective

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

    Design/Participants

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

    Results

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

    Conclusion

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

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  • 2.
    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
    University of Skövde, School of Health and Education. University of Skövde, Health and Education. 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 Syndrome2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 12, p. 4465-4477Article in journal (Refereed)
    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.

  • 3.
    Wolters, Maike
    et al.
    Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany.
    Marron, Manuela
    Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany.
    Foraita, Ronja
    Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany.
    Charalampos, Hadjigeorgiou
    Research and Education Institute of Child Health, Strovolos, Cyprus.
    De Henauw, Stefaan
    Department of Public Health and Primary Care, Ghent University, Belgium.
    Eiben, Gabriele
    University of Skövde, School of Health Sciences. University of Skövde, Digital Health Research (DHEAR). Department of Public Health and Community Medicine, University of Gothenburg Sweden.
    Lauria, Fabio
    Institute of Food Sciences, National Research Council, Avellino, Italy.
    Iglesia, Iris
    GENUD (Growth, Exercise, Nutrition and Development) Research Group, University of Zaragoza, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria de Aragón (IIS Aragón) Zaragoza, Spain ; Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Developmental Origin Network (RICORS), RD21/0012/0012, Instituto de Salud Carlos III, Madrid, Spain.
    Moreno, Luis A.
    GENUD (Growth, Exercise, Nutrition and Development) Research Group, University of Zaragoza, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria de Aragón (IIS Aragón) Zaragoza, Spain ; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain.
    Molnár, Dénes
    Department of Paediatrics, Medical School, University of Pécs, Hungary.
    Veidebaum, Toomas
    National Institute for Health Development, Tallinn, Estonia.
    Ahrens, Wolfgang
    eibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany ; Institute of Statistics, Faculty of Mathematics and Computer Science, Bremen University, Germany.
    Nagrani, Rajini
    Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany.
    IDEFICS and I.Family consortia,
    Longitudinal associations between vitamin D status and cardiometabolic risk markers among children and adolescents2023In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 108, no 12, p. e1731-e1742Article in journal (Refereed)
    Abstract [en]

    Background

    Vitamin D status has previously been associated with cardiometabolic risk markers in children and adolescents. In particular, it has been suggested that children with obesity are more prone to vitamin D deficiency and unfavorable metabolic outcomes compared to healthy-weight children. However, to date, there have been few longitudinal studies assessing this association in children stratified by BMI category.

    Methods

    Children from the pan-European IDEFICS/I.Family cohort with at least one measurement of serum 25-hydroxyvitamin D (25(OH)D) at cohort entry or follow-up (n=2,171) were included in this study. Linear mixed-effect models were used to assess the association between serum 25(OH)D as an independent variable and z-scores of cardiometabolic risk markers [waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), high (HDL) and low density lipoprotein, non-HDL, triglycerides (TRG), apolipoprotein A1 and B (ApoB), fasting glucose (FG), homeostatic model assessment for insulin resistance (HOMA-IR), metabolic syndrome score] as dependent variables.

    Results

    After adjustment for age, sex, study region, smoking and alcohol status, sports club membership, screen time, BMI, parental education, and month of blood collection, 25(OH)D levels were inversely associated with SBP, DBP, FG, HOMA-IR and TRG. The HOMA-IR z-score decreased by 0.07 units per 5 ng/ml increase in 25(OH)D. 25(OH)D was consistently associated with HOMA-IR irrespective of sex or BMI category.

    Conclusion

    Low serum 25(OH)D concentrations are associated with unfavorable levels of cardiometabolic markers in children and adolescents. Interventions to improve vitamin D levels in children with a poor status early in life may help to reduce cardiometabolic risk.

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