The Role of Androgens in Diet-Induced Microglial Activation and Metabolic Disease

Obesity is a global epidemic that is the leading risk factor for the development of adverse metabolic comorbidities including type 2 diabetes. Reduction of testosterone levels in men increases the risk of obesity and type 2 diabetes, which is reversed by testosterone administration. Despite increasing evidence in both clinical and epidemiological studies in humans, the mechanism by which a decline of testosterone contributes to increased adiposity remains largely unclear. Obesity is associated with activation of inflammatory cells called microglia in the hypothalamus, a brain region that controls appetite and metabolism. Since recent studies have demonstrated that reducing hypothalamic microglial inflammation prevents diet-induced obesity, and testosterone supports metabolic and immunological health in males, we hypothesized that the mechanism by which testosterone protects from metabolic disease involve a reduction of hypothalamic microglial inflammation induced by high-fat diet.