title: Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat.
abstract: To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 micrograms) 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 (-8%) 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 (-15%) and gastrointestinal fill (-50%) 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.
authors.affiliation: Department of Animal Physiology, University of Groningen, 9750 AA Haren, The Netherlands. g.van.dijk@bio.rug.nl
authors.forename: G
authors.initials: G
authors.lastname: van Dijk
authors.forename: R J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: T E
authors.initials: TE
authors.lastname: Thiele
authors.forename: M I
authors.initials: MI
authors.lastname: Friedman
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: C W
authors.initials: CW
authors.lastname: Wilkinson
authors.forename: P
authors.initials: P
authors.lastname: Burn
authors.forename: L A
authors.initials: LA
authors.lastname: Campfield
authors.forename: R
authors.initials: R
authors.lastname: Tenenbaum
authors.forename: D G
authors.initials: DG
authors.lastname: Baskin
authors.forename: S C
authors.initials: SC
authors.lastname: Woods
authors.forename: M W
authors.initials: MW
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects; D001786:Blood Glucose; D001835:Body Weight / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005223:Fats / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006003:Glycogen / Q000097:blood; D006120:Grooming / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D007328:Insulin / Q000097:blood; D020738:Leptin; D008297:Male; D010084:Oxidation-Reduction; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D012146:Rest / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005223:Fats; D007328:Insulin; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D011333:Pro-Opiomelanocortin; D006003:Glycogen; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone