title: Effect of leptin on hypothalamic GLP-1 peptide and brain-stem pre-proglucagon mRNA.
abstract: Leptin, the adipocyte-derived plasma hormone, and CNS GLP-1 neurons reduce food intake and body weight. GLP-1 is produced in the CNS by post-translational processing of pre-proglucagon. ICV leptin administration prevented the reduction in hypothalamic GLP-1 peptide content seen in pair-fed food-restricted rats (P < 0.05). There was a significant overall positive correlation between pre-proglucagon mRNA expression in the NTS and hypothalamic GLP-1 peptide content (r = +0.34, P < 0.05). Intraperitoneal leptin administration also increased hypothalamic GLP-1 peptide in food-restricted mice (P < 0. 05). This supports the hypothesis that the anorectic actions of leptin are in part due to stimulation of GLP-1 neurons. Reduced CNS GLP-1 neuronal activity during food deprivation may act to stimulate feeding behaviour, and perhaps also inhibit hypothalamic LHRH neurons, as part of the neuroendocrine response to starvation.
authors.affiliation: Endocrine Unit, Hammersmith Hospital, London, W12 0NN, United Kingdom.
authors.forename: A P
authors.initials: AP
authors.lastname: Goldstone
authors.forename: I
authors.initials: I
authors.lastname: Morgan
authors.forename: J G
authors.initials: JG
authors.lastname: Mercer
authors.forename: D G
authors.initials: DG
authors.lastname: Morgan
authors.forename: K M
authors.initials: KM
authors.lastname: Moar
authors.forename: M A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: S R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D005934:Glucagon / Q000235:genetics*; D052216:Glucagon-Like Peptide 1; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000235:genetics*; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020738:Leptin; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon