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

Research output: Contribution to journalArticle

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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
Externally publishedYes

Fingerprint

Agouti-Related Protein
Glucagon-Like Peptide 1
Corticotropin-Releasing Hormone
Amphetamine
Cocaine
Receptor, Melanocortin, Type 4
Appetite Depressants
Melanocyte-Stimulating Hormones
Eating
Leptin
agouti-related protein-(83-132)

Keywords

  • Anorectic
  • Food intake
  • Intracerebroventricular
  • Leptin
  • Melanocortin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cocaine- and amphetamine-regulated transcript, glucagon-like peptide-1 and corticotrophin releasing factor inhibit feeding via agouti-related protein independent pathways in the rat. / Edwards, C. M B; Abbott, Caroline R.; Sunter, David; Kim, Min Seon; Dakin, Catherine L.; Murphy, Kevin G.; Abusnana, Salah; Taheri, Shahrad; Rossi, Michela; Bloom, Stephen R.

In: Brain Research, Vol. 866, No. 1-2, 02.06.2000, p. 128-134.

Research output: Contribution to journalArticle

Edwards, C. M B ; Abbott, Caroline R. ; Sunter, David ; Kim, Min Seon ; Dakin, Catherine L. ; Murphy, Kevin G. ; Abusnana, Salah ; Taheri, Shahrad ; Rossi, Michela ; Bloom, Stephen R. / Cocaine- and amphetamine-regulated transcript, glucagon-like peptide-1 and corticotrophin releasing factor inhibit feeding via agouti-related protein independent pathways in the rat. In: Brain Research. 2000 ; Vol. 866, No. 1-2. pp. 128-134.
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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.",
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AU - Edwards, C. M B

AU - Abbott, Caroline R.

AU - Sunter, David

AU - Kim, Min Seon

AU - Dakin, Catherine L.

AU - Murphy, Kevin G.

AU - Abusnana, Salah

AU - Taheri, Shahrad

AU - Rossi, Michela

AU - Bloom, Stephen R.

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N2 - 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.

AB - 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.

KW - Anorectic

KW - Food intake

KW - Intracerebroventricular

KW - Leptin

KW - Melanocortin

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