Cocaine- and amphetamine-regulated transcript, glucagon-like peptide-1 and corticotrophin releasing factor inhibit feeding via agouti-related protein independent pathways in the rat

C. M.B. Edwards, Caroline R. Abbott, David Sunter, Min Seon Kim, Catherine L. Dakin, Kevin G. Murphy, Salah Abusnana, Shahrad Taheri, Michela Rossi, Stephen R. Bloom

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Abstract

The melanocortin-4 receptor (MC4-R) appears to be an important downstream mediator of the action of leptin. We examined to what extent the anorectic effects of cocaine- and amphetamine-regulated transcript (CART), glucagon-like peptide-1 (GLP-1) and corticotrophin releasing factor (CRF) might be mediated via MC4-R. α-Melanocyte stimulating hormone (α-MSH), the MC4-R agonist, administered intracerebroventricularly (ICV) at a dose of 1 nmol reduced food intake by approximately half. Agouti-related protein (Agrp) (83-132), a biologically active fragment of the endogenous MC4-R antagonist, administered ICV at a dose of 1 nmol completely blocked the anorectic effect of 1 nmol α-MSH. CART (55-102) (0.2 nmol), GLP-1 (3 nmol) and CRF (0.3 nmol) produced a reduction in feeding of approximately the same magnitude as 1 nmol α-MSH. Agrp (83-132) (1 nmol) administered ICV did not block the anorectic effects of CART (55-102) (1 h food intake, 0.2 nmol CART (55-102), 2.7±0.8 g vs. CART (55-102)+Agrp (83-132), 2.6±0.6 g, P=0.87; saline control 5.4±0.3 g, P<0.001 vs. both groups). Agrp (83-132) also did not block the anorectic effects of GLP-1 or CRF (1 h food intake, 0.3 nmol CRF, 0.7±0.3 g vs. CRF+Agrp (83-132), 0.7±0.3 g, P=0.91; 3 nmol GLP-1, 1.9±0.4 g vs. GLP-1+Agrp (83-132), 1.1±0.5 g, P=0.23; saline control 5.0±0.6 g, P<0.001 vs. all four groups). Thus, as previous data suggests, GLP-1 and CRF do not appear to reduce food intake predominantly via MC4-R, we here demonstrate for the first time that CART, in addition to GLP-1 and CRF primarily acts via Agrp independent pathways. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)128-134
Number of pages7
JournalBrain Research
Volume866
Issue number1-2
DOIs
Publication statusPublished - 2 Jun 2000

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Keywords

  • Anorectic
  • Food intake
  • Intracerebroventricular
  • Leptin
  • Melanocortin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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