Endoplasmic Reticulum Stress, the Hypothalamus, and Energy Balance

Overweight and obesity pose significant health problems globally, and are causatively linked to metabolic dysregulation. The hypothalamus integrates neural, nutritional, and hormonal cues to regulate homeostasis, including circadian rhythm, body temperature, thirst, food intake, energy expenditure, and glucose metabolism. Hypothalamic neuropeptides play a fundamental role in these processes. Studies during the past two decades suggest a role of central endoplasmic reticulum (ER) stress in the pathophysiology of obesity. This review covers recent findings on the role of ER stress and neuropeptide processing in the central regulation of energy homeostasis, with special emphasis on proopiomelanocortin (POMC)-encoding neurons. In addition, the role of neuroinflammation in the context of obesity is briefly discussed.