The Role of Microglia in the Development of Hypothalamic Feeding Circuits

Abstract

Exposure to high fat diet during the lactation period negatively affects body weight and the formation of hypothalamic feeding circuits. Neurons in the arcuate nucleus of the hypothalamus react to hormone secretion and distribute neuroendocrine information to other brain regions known to regulate food intake. During lactation, these neurons send their projections to several regions known to regulate metabolism outside the hypothalamus. Recent studies have shown that high fat diet in adults causes proliferation and activation of microglia. Microglia are the resident immune cells of the central nervous system that serve several important roles in regulating tissue homeostasis. They carry this role out by dynamically sampling the environment with complex processes and respond appropriately. Microglia are also known to be active regulators of neural circuit development in other regions. However, there has not yet been a proposed role for microglia in the development of hypothalamic feeding circuits. The premise of this project is that maternal high fat diet during lactation causes a regionally specific proliferation of microglia that perturbs the organization of hypothalamic feeding circuits, associated with permanent disruption of metabolic phenotype in offspring.