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 posttranslatio nal processing of pre-proglucagon. ICV leptin administration prevented the reduction in hypothalamic GLP-1 peptide content seen in pair-fed food-restr icted 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 administrati on 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; a ctivity during food deprivation may act to stimulate feeding behaviour, and perhaps also inhibit hypothalamic LHRH neurons, as part of the neuroendocr ine response to starvation. (C) 2000 Academic Press.