Metabolic factors in the regulation of hypothalamic innate immune responses in obesity

The hypothalamus is a central regulator of body weight and energy homeostasis. There is increasing evidence that innate immune activation in the mediobasal hypothalamus (MBH) is a key element in the pathogenesis of diet-induced obesity. Microglia, the resident immune cells in the brain parenchyma, have been shown to play roles in diverse aspects of brain function, including circuit refinement and synaptic pruning. As such, microglia have also been implicated in the development and progression of neurological diseases. Microglia express receptors for and are responsive to a wide variety of nutritional, hormonal, and immunological signals that modulate their distinct functions across different brain regions. We showed that microglia within the MBH sense and respond to a high-fat diet and regulate the function of hypothalamic neurons to promote food intake and obesity. Neurons, glia, and immune cells within the MBH are positioned to sense and respond to circulating signals that regulate their capacity to coordinate aspects of systemic energy metabolism. Here, we review the current knowledge of how these peripheral signals modulate the innate immune response in the MBH and enable microglia to regulate metabolic control.