1. Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Degree Relatives of Patients With Type 2 Diabetes
- Author
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Nils Wierup, Emma Nilsson, Ola Hansson, Peter Almgren, Stefan Lang, Ylva Wessman, Elin Hall, Targ Elgzyri, Beatrice T. Yang, Holger Weishaupt, Leif Groop, Peter Volkov, Hemang Parikh, Marloes Dekker Nitert, Mia Abels, Tina Rönn, Tasnim Dayeh, Karl-Frederik Eriksson, Charlotte Ling, Joanne L. Attema, and Per-Anders Jansson
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Monozygotic twin ,MADS Domain Proteins ,Biology ,Protein Serine-Threonine Kinases ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Epigenetics ,MAPK1 ,Muscle, Skeletal ,Gene ,Exercise ,MEF2 Transcription Factors ,Intracellular Signaling Peptides and Proteins ,Skeletal muscle ,Genetics/Genomes/Proteomics/Metabolomics ,Epigenome ,Methylation ,DNA Methylation ,Neoplasm Proteins ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 2 ,Myogenic Regulatory Factors ,DNA methylation ,Core Binding Factor Alpha 2 Subunit ,Receptors, Adiponectin - Abstract
To identify epigenetic patterns, which may predispose to type 2 diabetes (T2D) due to a family history (FH) of the disease, we analyzed DNA methylation genome-wide in skeletal muscle from individuals with (FH+) or without (FH−) an FH of T2D. We found differential DNA methylation of genes in biological pathways including mitogen-activated protein kinase (MAPK), insulin, and calcium signaling (P ≤ 0.007) and of individual genes with known function in muscle, including MAPK1, MYO18B, HOXC6, and the AMP-activated protein kinase subunit PRKAB1 in skeletal muscle of FH+ compared with FH− men. We further validated our findings from FH+ men in monozygotic twin pairs discordant for T2D, and 40% of 65 analyzed genes exhibited differential DNA methylation in muscle of both FH+ men and diabetic twins. We further examined if a 6-month exercise intervention modifies the genome-wide DNA methylation pattern in skeletal muscle of the FH+ and FH− individuals. DNA methylation of genes in retinol metabolism and calcium signaling pathways (P < 3 × 10−6) and with known functions in muscle and T2D including MEF2A, RUNX1, NDUFC2, and THADA decreased after exercise. Methylation of these human promoter regions suppressed reporter gene expression in vitro. In addition, both expression and methylation of several genes, i.e., ADIPOR1, BDKRB2, and TRIB1, changed after exercise. These findings provide new insights into how genetic background and environment can alter the human epigenome.
- Published
- 2012