Microglia are emerging as critical regulators of brain homeostasis with an expanding array of functions beyond their established roles as immune sentinels such as synaptic remodeling, neuronal excitability, and myelin plasticity. These highly dynamic cells continuously monitor their microenvironment for alterations, and distinct populations and activation states have been identified based on brain anatomical location, sex, and age. While microglia can respond to both local cues and peripheral factors, the complete repertoire of signals and transduction cascades governing their function remains to be elucidated. We recently showed that microglia are involved in the hypothalamic regulation of energy and glucose homeostasis. However, the cellular and molecular mechanisms by which microglial dysfunction contributes to metabolic disease are poorly understood. Our laboratory is dedicated to unraveling the functional heterogeneity of microglia, exploring their regulation by nutritional and metabolic signals, and understanding their interactions with other glial cells and neurons in the control of metabolic function