title: Hypothalamic CART is a new anorectic peptide regulated by leptin.
abstract: The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.
authors.affiliation: Health Care Discovery, Novo Nordisk, Bagsvaerd, Denmark. pekr@novo.dk
authors.forename: P
authors.initials: P
authors.lastname: Kristensen
authors.forename: M E
authors.initials: ME
authors.lastname: Judge
authors.forename: L
authors.initials: L
authors.lastname: Thim
authors.forename: U
authors.initials: U
authors.lastname: Ribel
authors.forename: K N
authors.initials: KN
authors.lastname: Christjansen
authors.forename: B S
authors.initials: BS
authors.lastname: Wulff
authors.forename: J T
authors.initials: JT
authors.lastname: Clausen
authors.forename: P B
authors.initials: PB
authors.lastname: Jensen
authors.forename: O D
authors.initials: OD
authors.lastname: Madsen
authors.forename: N
authors.initials: N
authors.lastname: Vrang
authors.forename: P J
authors.initials: PJ
authors.lastname: Larsen
authors.forename: S
authors.initials: S
authors.lastname: Hastrup
mesh_terms: D000818:Animals; D000855:Anorexia / Q000378:metabolism*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D003001:Cloning, Molecular; D004926:Escherichia coli; D005215:Fasting; D005247:Feeding Behavior / Q000502:physiology; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology*; D007124:Immunoenzyme Techniques; D020738:Leptin; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein