Exercise As a Therapeutic Approach to Reduce Maternal and Paternal Diet-Induced Type 2 Diabetes Mellitus (T2DM) Risk

Maternal and paternal over- and undernutrition increase, while exercise decreases, offspring risk of obesity and T2DM. No studies have yet to determine how parental diets interact with parental exercise to epigenetically alter the number of offspring white and beige adipocytes and skeletal muscle tissue metabolic pathways to regulate obesity and T2DM risk. Using a maternal undernutrition model, we fed obese-prone Sprague-Dawley rats maternal low protein (LP) or normal protein diets and post-weaning fed the offspring a normal or high fat (HF) diet for 3 months. Maternal LP combined with post-weaning HF diets increased offspring T2DM risk by 1) increasing subcutaneous adipose tissue growth rate via increased insulin growth factor 2 (Igf2) gene DNA methylation, 2) decreasing skeletal muscle mitochondrial oxygen consumption rate and increasing the inactive form (SDH-acetylated form) of succinate dehydrogenase and, 3) by reducing numbers of beige adipocytes and thermogenesis in the subcutaneous adipose tissue and by increasing histone methyltransferase (G9a). For over nutrition studies, C57BL/6 male mice were fed a paternal normal or HF diet with or without voluntary wheel running for 3 months and the offspring were fed HF or control diets for 3 months. The offspring born of fathers fed a HF diet and exercised had lower body weight and body fat without any effect on T2DM risk. The reduction in fat % with no change in T2DM risk was accounted for by improved skeletal muscle insulin signaling. These findings suggest that the benefits of paternal exercise are most readily expressed in offspring challenged with a postnatal HF diet. Future studies are needed to determine the role of epigenetic mechanisms and alterations that regulate metabolic processes in adipose and skeletal muscle tissues, and how these epigenetic alterations might be transmitted to subsequent generations.