Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome

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Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome

Nilsson, Emma (author): Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital

Benrick, Anna, 1979 (author): University of Skövde,University of Gothenburg,Högskolan i Skövde,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden; Univ Skövde, Sch Hlth & Educ, Skövde, Sweden,Institutionen för hälsa och lärande,Forskningsspecialiseringen Hälsa och Lärande,Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,Translationell medicin (TRIM), Translational Medicine

Kokosar, Milana (author): University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden,Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Krook, A. (author): Karolinska Institutet

Lindgren, E. (author): Karolinska Institutet

Källman, Thomas, 1976- (author): Uppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden,Department of Medical Biochemistry and Microbiology, National Bioinformatics Infrastructure Sweden, SciLifeLab, Uppsala University, Uppsala, Sweden

Martis-Thiele, Mihaela-Maria (author): Linköping University,Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,National Bioinformatics Infrastructure Sweden, Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Hojlund, K. (author): Odense Univ, Dept Endocrinol, Odense C, Denmark,Department of Endocrinology, Odense University, Odense C, Denmark,University of Southern Denmark

Ling, Charlotte (author): Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital

Stener-Victorin, E. (author): Karolinska Institutet

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(creator_code:org_t)

2018-08-02
2018
English.
In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:12, s. 4465-4477

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Journal article (peer-reviewed)

Abstract Subject headings

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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)

Keyword

human adipose-tissue
hla-g
glucose-metabolism
insulin-resistance
glycogen-synthase
DNA methylation
human myotubes
expression
phosphorylation
klf10
Endocrinology & Metabolism
Translationell medicin TRIM

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ref (subject category)
art (subject category)

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