Central role of the melanocortin-4 receptors in appetite regulation after endotoxin

J. L. Sartin, Daniel Marks, C. D. McMahon, J. A. Daniel, P. Levasseur, C. G. Wagner, B. K. Whitlock, B. P. Steele

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Melanocortin-4 receptors (MC4R) are key factors in the depression of appetite during disease. This study was designed to determine the role of agouti-related protein (AgRP) in the effect of endotoxin (lipopolysaccharide, LPS) on appetite. Sheep received an intracerebroventricular injection of either saline or AgRP (0.5 nmol/kg of BW) 1 h before intravenous injection of either saline or LPS (0.6 pg/kg of BW) at time O and again at 4 h. Agouti-related protein prevented the reduction in feed intake due to LPS (P <0.05). In a second experiment, AgRP gene expression was unaffected at 3 h and increased (P <0.01) at 6 h after LPS. Immunohistochemical evidence indicated that there was an increase in the percentage of AgRP neurons with c-Fos immunoreactive nuclei 6 h after sheep were injected with LPS (P <0.04) and a corresponding decrease in α-melanocyte-stimulating hormone neurons coexpressing c-Fos (P <0.001). In situ hybridization provided evidence for an increase in AgRP gene expression and a decrease in proopiomelanocortin gene expression 6 h after LPS (P <0.05). In a final experiment, physiological elevation of orexigenic agents by short-term fasting kept feed intake at the same level as controls, in spite of the presence of LPS, similar to the effects of AgRP in Exp. 1. The AgRP inhibition of the MC4R prevents appetite inhibition in response to LPS and well after LPS inhibition of feed intake, both AgRP and α-melanocyte- stimulating hormone may change in a pattern that favors appetite increases. These studies support the notion of the MC4R as a critical component of the mechanism for appetite suppression due to endotoxin.

Original languageEnglish (US)
Pages (from-to)2557-2567
Number of pages11
JournalJournal of Animal Science
Volume86
Issue number10
DOIs
StatePublished - Oct 2008

Fingerprint

Agouti-Related Protein
Receptor, Melanocortin, Type 4
Appetite Regulation
Agouti
endotoxins
appetite
Endotoxins
lipopolysaccharides
Lipopolysaccharides
receptors
Appetite
proteins
melanocyte-stimulating hormone
Melanocyte-Stimulating Hormones
feed intake
Gene Expression
gene expression
Sheep
neurons
pro-opiomelanocortin

Keywords

  • A-melanocyte-stimulating hormone
  • Agouti-related protein
  • Food intake
  • Hypothalamus
  • Melanocortin-4 receptor
  • Sheep

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Food Science
  • Genetics

Cite this

Sartin, J. L., Marks, D., McMahon, C. D., Daniel, J. A., Levasseur, P., Wagner, C. G., ... Steele, B. P. (2008). Central role of the melanocortin-4 receptors in appetite regulation after endotoxin. Journal of Animal Science, 86(10), 2557-2567. https://doi.org/10.2527/jas.2008-0916

Central role of the melanocortin-4 receptors in appetite regulation after endotoxin. / Sartin, J. L.; Marks, Daniel; McMahon, C. D.; Daniel, J. A.; Levasseur, P.; Wagner, C. G.; Whitlock, B. K.; Steele, B. P.

In: Journal of Animal Science, Vol. 86, No. 10, 10.2008, p. 2557-2567.

Research output: Contribution to journalArticle

Sartin, JL, Marks, D, McMahon, CD, Daniel, JA, Levasseur, P, Wagner, CG, Whitlock, BK & Steele, BP 2008, 'Central role of the melanocortin-4 receptors in appetite regulation after endotoxin', Journal of Animal Science, vol. 86, no. 10, pp. 2557-2567. https://doi.org/10.2527/jas.2008-0916
Sartin, J. L. ; Marks, Daniel ; McMahon, C. D. ; Daniel, J. A. ; Levasseur, P. ; Wagner, C. G. ; Whitlock, B. K. ; Steele, B. P. / Central role of the melanocortin-4 receptors in appetite regulation after endotoxin. In: Journal of Animal Science. 2008 ; Vol. 86, No. 10. pp. 2557-2567.
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