Hypothalamic inflammation and the central nervous system control of energy homeostasis

• Inflammation coordinates hypothalamic set point adaptation.
• Low-grade hypothalamic inflammation promotes obesity.
• Hypothalamic inflammation leads to insulin and leptin resistance.
• High-grade hypothalamic inflammation induces anorexia.

The control of energy homeostasis relies on robust neuronal circuits that regulate food intake and energy expenditure. Although the physiology of these circuits is well understood, the molecular and cellular response of this program to chronic diseases is still largely unclear. Hypothalamic inflammation has emerged as a major driver of energy homeostasis dysfunction in both obesity and anorexia. Importantly, this inflammation disrupts the action of metabolic signals promoting anabolism or supporting catabolism. In this review, we address the evidence that favors hypothalamic inflammation as a factor that resets energy homeostasis in pathological states.