Effects of Physical Exercise on Mitochondrial Biogenesis of Skeletal Muscle Modulated by Histones Modifications in Type 2 Diabetes

Hellen Barbosa; Wael Ramadan; Júlia Matzenbacher dos Santos; Sandra Aparecida Benite-Ribeiro

doi:10.3889/oamjms.2022.10095

Authors

Hellen Barbosa Pós-Graduação em Biociência Animal, Universidade Federal de Jataí, Jataí, Goiás, Brazil
Wael Ramadan Department of Sports Training
Júlia Matzenbacher dos Santos Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, PA, United States
Sandra Aparecida Benite-Ribeiro Unidade Acadêmica Especial de Ciências Biológicas, Universidade Federal de Jataí, Goiás, Brazil

DOI:

https://doi.org/10.3889/oamjms.2022.10095

Keywords:

AMP-activated protein kinase, ATP-citrate lyase, Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, Oxidative stress, Inflammation

Abstract

Epigenetic modification in skeletal muscle induced by environmental factors seems to modulate several metabolic pathways that underlie Type 2 Diabetes Mellitus (T2DM) development. Mitochondrial biogenesis is an important process for maintaining lipid metabolism homeostasis, as well as epigenetic modifications in proteins that regulate this pathway have been observed in the skeletal muscle of T2DM subjects. Moreover, physical exercise affects several metabolic pathways attenuating metabolic deregulation observed in T2DM. The pathways that regulate mitochondrial homeostasis are one of the key components for understanding such physical exercise beneficial effects. Thus, in this study, we investigate the epigenetic mechanisms underlying mitochondrial biogenesis in the skeletal muscle in T2DM, focusing on histone modifications and the possible mechanisms by which physical exercise delay or inhibit T2DM onset. The results indicate that exercise promotes improvements in cellular metabolism through increasing enzymes of the antioxidant system, AMPK and ATP-citrate lyase activity, Acetyl-CoA concentration, and enhancing the acetylation of histones. A key mediator of mitochondrial biogenesis such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC1) seems to be upregulated by exercise in T2DM and such factor positively regulates the skeletal muscle mitochondrial biogenesis, which improves energy metabolism and glucose homeostasis inhibiting or delaying insulin resistance and further T2DM.

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