Hyperpalatable diet and physical exercise affects the brain metabolism : role of the brain lactate shuttle

Abstract

Diet rich in fat and sugar associated to sedentary habits are the main cause of obesity. Obesity is a risk factor for the development of insulin resistance and diabetes. Insulin receptors and signaling modulates brain energetic metabolism. However, brain insulin resistance is associated with cognitive deficits and neurodegeneration. Lactate is an important energetic substrate to brain in specific situations; it is transported by monocarboxylate transporters (MCTs), which are regulated by many factors including insulin signaling. Hyperpalatable diet (HP) impairs brain insulin signaling whereas physical exercise improves insulin signaling and cognition function. We evaluated the effects of four months of HP diet followed by one month of physical exercise plus HP diet in MCT expression, lactate levels on hippocampus and brain mitochondrial function. Male C57BL/J6 mice, 1 month old were divided in the following groups: control diet sedentary (CDS), control diet exercise (CDE), HP diet sedentary (HPS), and HP diet exercise (HPE) (n=15 per group). Lactate extracellular brain fluid was increased in HPE group after Y-maze task when compared to other groups. The MCT-1 and 4 levels increased in exercise and HP diet groups. The hydrogen peroxide (H2O2) production stimulated by succinate in homogenate of hippocampus was increased in HPS group. Incubation of insulin (0.1 ug/mL) reduced the H2O2 production in all groups. In summary, these results showed that a HP diet increases MCT expression, affects brain lactate shuttle and mitochondrial function. However, voluntary physical exercise revert the negative effects of HP diet in this brain metabolic outcomes.