Effect of leptin administration versus re-feeding on hypothalamic neuropeptide gene expression in fasted male rats

Adipocytes are the primary source of circulating leptin. Leptin inhibits eating, increases metabolism, and stimulates the reproductive axis. Numerous hypothalamic neuropeptides have been implicated in leptin's behavioral and neuroendocrine effects, including neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART). The aim of this study was to investigate the physiological relevance of leptin's signaling of nutritional status by comparing the effects of leptin with the effects of re-feeding on fasting-induced changes in the expression of the long form of the leptin receptor (Ob-Rb), NPY, and CART. Adult male rats were fasted for 48 h and treated with either intracerebroventricular (i.c.v.) or subcutaneous (s.c.) leptin throughout the fast, or fed ad libitum for 24 h after terminating the fast. Expression of NPY, Ob-Rb, and CART mRNA in the arcuate nucleus (ARC) was determined by in situ hybridization histochemistry and compared with vehicle-treated fed or fasted controls. Fasting increased NPY and Ob-Rb expression and decreased CART expression in the ARC. Leptin (regardless of route) and re-feeding were equally effective in normalizing CART mRNA expression. A similar trend was observed with Ob-Rb expression. In contrast, neither re-feeding nor s.c. leptin reversed the increased expression of NPY that was induced by fasting. Only i.c.v. leptin was effective in this regard. Our results indicate leptin and re-feeding are equally effective in normalizing fasting-induced changes in CART and Ob-Rb expression, but less effective in normalizing NPY expression. These results suggest that leptin is the primary nutritional signal regulating CART and Ob-Rb expression in the ARC, and highlight potential differences between CART and NPY neuron sensitivity to leptin signaling.