Targeting Hypothalamic Microglia to Regulate Glucose Homeostasis
Metabolic diseases that traditionally are linked to inappropriate lifestyle of adults, such as type 2 diabetes, can be “programmed” in the early stage of life due to structural changes and modifications of metabolic function of some organs, such as the brain. We showed that microglia accumulate in the hypothalamus, a part of the brain that controls both body weight and glucose control, during neonatal life when mammals rely solely on milk rich in saturated fat, and that these microglia are required for normal blood glucose control later in life. Based on our recent findings and our expertise in relevant cutting-edge techniques, we propose to investigate the capacity of neonatal microglia to program the hypothalamic regulation of blood glucose in adulthood. Our goal is defining the capacity of neonatal microglia to program specific neuronal circuits regulating blood glucose and determine the cellular and molecular mechanisms by which early life microglia impact adult glucose metabolism. These studies are expected to provide a greater mechanistic understanding of the role of microglia in the adaptive early life programming of adult hypothalamic function in the regulation of glucose metabolism with the potential to uncover new therapeutic targets for the prevention and treatment of type 2 diabetes.