Can Exercise Training Alter Human Skeletal Muscle DNA Methylation?

Luis A Garcia,Yassin Hamzaoui,Judith Krentzel,Linda Wu,Rocio Zapata-Bustos,Dawn K Coletta,Lori R Roust,Alma D Leon,Richard L Coletta,Baltazar Campos,Lawrence J Mandarino,Samantha E Day,Eleanna De Filippis

doi:10.3390/metabo12030222

Abstract

Skeletal muscle is highly plastic and dynamically regulated by the body’s physical demands. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to 8 weeks of supervised exercise training in volunteers with a range of insulin sensitivities. We studied 13 sedentary participants and performed euglycemic hyperinsulinemic clamps with basal vastus lateralis muscle biopsies and peak aerobic activity (VO2 peak) tests before and after training. We extracted DNA from the muscle biopsies and performed global methylation using Illumina’s Methylation EPIC 850K BeadChip. Training significantly increased peak aerobic capacity and insulin-stimulated glucose disposal. Fasting serum insulin and insulin levels during the steady state of the clamp were significantly lower post-training. Insulin clearance rates during the clamp increased following the training. We identified 13 increased and 90 decreased differentially methylated cytosines (DMCs) in response to 8 weeks of training. Of the 13 increased DMCs, 2 were within the following genes, FSTL3, and RP11-624M8.1. Of the 90 decreased DMCs, 9 were within the genes CNGA1, FCGR2A, KIF21A, MEIS1, NT5DC1, OR4D1, PRPF4B, SLC26A7, and ZNF280C. Moreover, pathway analysis showed an enrichment in metabolic and actin-cytoskeleton pathways for the decreased DMCs, and for the increased DMCs, an enrichment in signal-dependent regulation of myogenesis, NOTCH2 activation and transmission, and SMAD2/3: SMAD4 transcriptional activity pathways. Our findings showed that 8 weeks of exercise training alters skeletal muscle DNA methylation of specific genes and pathways in people with varying degrees of insulin sensitivity.

Highlights

Licensee MDPI, Basel, Switzerland.The physical demands of the body dynamically regulate skeletal muscle
There were no changes at a global level, we identified novel differentially methylated cytosines (DMCs) that were changing with the exercise intervention using several filtering methods
In addition to the pathways described above, we identified several candidate genes (FSTL3, RP11-624M8.1, CNGA1, FCGR2A, Kinesin Family Member 21A (KIF21A), Meis Homeobox 1 (MEIS1), NT5DC1, OR4D1, Pre-mRNA Processing Factor 4B (PRPF4B), SLC26A7, and Zinc Finger Protein 280C (ZNF280C)) that merit a discussion

Summary

Introduction

The physical demands of the body dynamically regulate skeletal muscle. It is a highly plastic tissue adaptable to many stimuli, such as contractile activity. Kirwan et al recently discussed the metabolic effects of acute and chronic exercise changes [1]. The acute effects of exercise (i.e., a single bout of exercise) include immediate improvements in blood glucose levels and increased insulin sensitivity at the muscle tissue [1]. The chronic effects of exercise include increased skeletal muscle expression of genes coding for muscle published maps and institutional affil-

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