Effect of leptin on hypothalamic GLP-1 peptide and brain-stem pre-proglucagon mRNA

Biochem Biophys Res Commun. 2000 Mar 16;269(2):331-5. doi: 10.1006/bbrc.2000.2288.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Stem / drug effects*
  • Brain Stem / metabolism
  • Glucagon / genetics*
  • Glucagon-Like Peptide 1
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Injections, Intraventricular
  • Leptin / administration & dosage
  • Leptin / pharmacology*
  • Male
  • Peptide Fragments / genetics*
  • Proglucagon
  • Protein Precursors / genetics*
  • RNA, Messenger / genetics*
  • Radioimmunoassay
  • Rats
  • Rats, Wistar


  • Leptin
  • Peptide Fragments
  • Protein Precursors
  • RNA, Messenger
  • Proglucagon
  • Glucagon-Like Peptide 1
  • Glucagon