Effect of leptin on hypothalamic GLP-1 peptide and brain-stem pre-proglucagon mRNA.
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.
Goldstone
A P
AP
Endocrine Unit, Hammersmith Hospital, London, W12 0NN, United Kingdom.
Morgan
I
I
Mercer
J G
JG
Morgan
D G
DG
Moar
K M
KM
Ghatei
M A
MA
Bloom
S R
SR
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
D020738:Leptin; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon