Hypothalamic hypocretin/orexin and neuropeptide Y: Divergent interaction with energy depletion and leptin

The aim of this study was to measure the effects of chronic leptin treatmen t on two orexigenic peptides present in the hypothalamus namely hypocretin/ orexin and neuropeptide Y (NPY), For this purpose, recombinant murine lepti n (0.2 mg/rat/day) or saline were injected intraperitoneally in Long-Evans rats for 7 consecutive days. Food intake (-8%; p < 0.002) and body weight g ain (23.7 +/- 1 vs 31.5 +/- 1.3 g; p < 0.003) were significantly lower in l eptin-treated rats than the saline-treated rats. NPY concentrations did not change significantly in any of the microdissected brain areas including th e arcuate and paraventricular nuclei. Orexin A concentration in the lateral hypothalamus was significantly decreased by the leptin treatment (-68%; p < 0.01). A smaller decrease (-46%; p < 0.04) was also noted in saline-treat ed rats pairfed to the level of the leptin-treated rats. We conclude that o rexin/hypocretin could be considered as a new relay for leptin in the centr al nervous system. Its variation in case of lower energy supply observed in pairfed rats could constitute an alerting system for the brain and therefo re considered as the first step in the establishment of defense mechanisms against energy depletion. (C) 1999 Academic Press.