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Effect of Leptin on Hypothalamic GLP-1 Peptide and Brain-Stem Pre-proglucagon mRNA

https://doi.org/10.1006/bbrc.2000.2288Get rights and content

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 expreession 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.

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    Abbreviations used: α-MSH, α-melanocyte stimulating hormone; CNS, central nervous system; CRH, corticotropin-releasing hormone; GLP-1, glucagon-like peptide-1 (7–36) amide; ICV, intracerebroventricular; IP, intraperitoneal; MC4R, melanocortin-4 receptor; NPY, neuropeptide Y; NTS, nucleus of the solitary tract; OBRb, long isoform of leptin receptor

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