Physical Exercise and Epigenetic Modulation: Elucidating Intricate Mechanisms

Physical exercise induces several metabolic adaptations to meet increased energy requirements. Promoter DNA methylation, histone post-translational modifications, or microRNA expression are involved in the gene expression changes implicated in metabolic adaptation after exercise. Epigenetic modifications and many epigenetic enzymes are potentially dependent on changes in the levels of metabolites, such as oxygen, tricarboxylic acid cycle intermediates, 2-oxoglutarate, 2-hydroxyglutarate, and β-hydroxybutyrate, and are therefore susceptible to the changes induced by exercise in a tissue-dependent manner. Most of these changes are regulated by important epigenetic modifiers that control DNA methylation (DNA methyl transferases, and ten–eleven-translocation proteins) and post-translational modifications in histone tails controlled by histone acetyltransferases, histone deacetylases, and histone demethylases (jumonji C proteins, lysine-specific histone demethylase, etc.), among others. Developments in mass spectrometry approaches and the comprehension of the interconnections between epigenetics and metabolism further increase our understanding of underlying epigenetic mechanisms, not only of exercise, but also of disease and aging. In this article, we describe several of these substrates and signaling molecules regulated by exercise that affect some of the most important epigenetic mechanisms, which, in turn, control the gene expression involved in metabolism.