Neuropeptide Y in central control of feeding and interactions with orexin and leptin

Neuropeptide (NPY) increases feeding when injected into the brain. In this study, we tested the hypothesis that its action might be related to feeding regulation of the orexin and leptin systems in rats. Intracerebroventricul ar administration of NPY (1 nmol/5 muL) stimulated feeding in rats. Injecti on of an antibody to orexin-A inhibited feeding, suggesting that endogenous orexin exerts a stimulatory tone on feeding. Intracerebroventricular injec tion of orexin antiserum before injection of NPY significantly attenuated t he feeding response to NPY, On the other hand, ip pretreatment with leptin (2 mg/kg) significantly decreased food intake and inhibited NPY-induced fee ding. We then examined whether orexin-containing neurons are activated unde r the stimulation of feeding in response to intracerebroventricular NPY or suppression of feeding in response to ip leptin, using Fos-like immunoreact ivity (FLI) as a marker of neural activation. We observed that FLI was indu ced in the paraventricular, supraoptic, and dorsomedial nuclei as well as t he lateral hypothalamic area (LHA) following administration of NPY, Double staining with anti-fos and anti-orexin antibodies revealed that 23.4% of th e orexin-containing neurons in the LHA expressed FLI after NPY injection. A pproximately 7.8% of the orexin-positive neurons in the LHA coexpressed Fos after leptin plus NPY, Our data indicate that a functional interaction amo ng NPY, orexin, and leptin exists that may contribute to the central regula tion of appetite.