Type 2 diabetes, the leading metabolic disease, is characterized by insulin resistance and is associated with obesity. The onset of type 2 diabetes is largely due to environmental inputs, such as high dietary fat content and decreased levels of exercise. Insulin resistance resulting from high fat diet is associated with skeletal muscle mitochondrial dysfunction, leading to alterations in lipid accumulation and specific species of intracellular fatty acids; whereas, exercise training augments insulin resistance while improving skeletal muscle mitochondrial function and producing beneficial fatty acid profiles. Additionally, high fat diets and exercise alter epigenetic modifications, including DNA methylation and histone acetylation, to produce differences in metabolic gene expression that are associated with insulin resistance and sensitivity, respectively. Recent evidence suggests that short chain fatty acids that act as histone deacetylase inhibitors prevent and ameliorate obesity and insulin resistance. Here, we discuss the potential of mitochondrial-derived fatty acids, especially short chain fatty acids, to epigenetically regulate obesity and type 2 diabetes.
Keywords: Diabetes; Epigenetics; Fatty acids; Mitochondria; Obesity.