The hypothalamus is the primary area of the central nervous system (CNS) involved in regulating energy intake and energy expenditure. The arcuate nucleus (ARC) of the mediobasal hypothalamus incorporates signals from adipose tissue and the gastrointestinal tract to communicate nutritional status, energy stores, and hunger/satiety. These peripheral signals include insulin, leptin, and gut hormones such as glucagon-like peptide-1 (GLP-1), the hormone targeted by the new generation of antiobesity medications. The ARC comprises two main sets of neurons, the orexigenic (stimulating food intake) and anorexigenic (inhibiting food intake) neurons that counterbalance each other and that mediate the effects of leptin and insulin. The anorexigenic neurons of the ARC produce proopiomelanocortin (POMC), which is converted to alpha-melanocyte–stimulating hormone (MSH). Alpha MSH acts on the melanocortin-4 receptor (MC4R) to reduce food intake and increase energy expenditure, and can be deficient in some genetic disorders.
Hypothalamic Obesity With Specific Pathology
Obesity associated with hypothalamic dysfunction was initially described in patients with craniopharyngioma. Hypothalamic obesity may also result from brain radiation, infection (eg, tuberculosis), autoimmune disease (eg, sarcoidosis), or traumatic brain injury. Thus, clinicians should suspect a hypothalamic component in patients presenting with obesity plus a history of one of these conditions.
In some patients, a hallmark sign of hypothalamic obesity is
