Van Dijk, GertjanSeely, Randy J.Thiele, Todd E.Friedman, Mark I.Ji, HongWilkinson, Charles W.Burn, PaulCampfield, ArthurTenenbauim, RenataRaskin, Denis G.Woods, Stephen C.2011-11-232011-11-231999http://hdl.handle.net/1773/19327Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R1425–R1433, 1999.—To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 μg) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to leptin-induced anorexia, we studied vehicle-infused rats with food available ad libitum and those that were pair-fed to leptin-treated animals. Although body weight was comparably reduced (28%) and plasma glycerol was comparably increased (142 and 17%, respectively) in leptin-treated and pair-fed animals relative to controls, increases in plasma fatty acids and ketones were only detected (132 and 234%, respectively) in pair-fed rats. Resting energy expenditure (215%) and gastrointestinal fill (250%) were reduced by pair-feeding relative to the ad libitum group, but they were not reduced by leptin treatment. Relative to controls, leptin increased hypothalamic mRNA for corticotropin-releasing hormone (CRH; 61%) and for proopiomelanocortin (POMC; 31%) but did not reduce mRNA for neuropeptide Y. These results suggest that CNS leptin prevents metabolic/gastrointestinal responses to caloric restriction by activating hypothalamic CRH- and POMC-containing pathways and raise the possibility that these peripheral responses to CNS leptin administration contribute to leptin’s anorexigenic action.enOB Proteinsympathetic nervous systemcorticotropinreleasinghormoneproopiomelanocortin;food intakeArticle