Role of Mitochondria in Brain Nutrient Sensing: Control of Energy Balance and Dysregulation in Obesity and Type 2 Diabetes

Abstract During the last 20 years, studies have revealed the important role of the central nervous system (CNS) in the regulation of homeostatic mechanisms, including food intake, energy expenditure, and glucose, lipid and protein homeostasis. Brain regions involved in the regulation of energy balance, such as the arcuate (ARC), the ventromedial nuclei of the hypothalamus (VMN), and the hindbrain, have the ability to monitor the amount of available fuel in the body, to modulate energy intake and expenditure, and to modify peripheral tissue/organ function via alteration of neuronal firing. For that, they must be informed about the level of nutrients. Within specific brain sites, neuronal populations have been described as able to sense all types of nutrients, enabling proper peripheral tissue adaptations to the fluctuating nutrient environment. Therefore, when glucose or fatty acids rise in the blood because of food consumption, specific brain circuits promote cessation of feeding (satiety), insulin secretion, and glucose use by peripheral tissues while inhibiting hepatic glucose production. When the level of glucose decreases between meals, however, another set of neurons is activated to promote hunger and appropriate changes in peripheral glucose and lipid metabolisms.