Leptin action in the forebrain regulates the hindbrain response to satiety signals

摘要: The capacity to adjust energy intake in response changing requirements is a defining feature of homeostasis. Despite the identification leptin as key mediator this process, mechanism whereby changes body adiposity are coupled adaptive, short-term adjustments remains poorly understood. To investigate physiological role control meal size and satiety signals, identify brain areas mediating effect, we studied Koletsky (fa(k)/fa(k)) rats, which develop severe obesity due genetic absence receptors. Our finding markedly increased reduced gut peptide cholecystokinin (CCK) these receptor-deficient animals suggests critical for signaling endogenous signals that promote termination. determine if hypothalamic arcuate nucleus (ARC) (a forebrain site action) mediates used adenoviral gene therapy express either functional receptors or reporter area ARC fa(k)/fa(k) rats. Restoration normalized effect CCK on activation neurons solitary tract postrema, hindbrain processing satiety-related inputs. This intervention also enhanced CCK-induced These findings demonstrate by leptin, long-term regulator adiposity, limits food meal-to-meal basis regulating short-acting signals.