Differential role of melanocortin receptor subtypes in cachexia

Daniel Marks, Andrew A. Butler, Renn Turner, Gregor Brookhart, Roger D. Cone

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Animals and humans respond to starvation with a complex neuroendocrine response that ultimately leads to an increase in appetite, a sparing of lean body mass (LBM) and burning of fat, and an overall decrease in basal metabolic rate. In contrast, cachexia is a pathological state of malnutrition associated with many infections and chronic diseases, wherein appetite is diminished concomitant with an increase in metabolic rate, and a relative wasting of LBM. In previous studies, we demonstrated that anorexia and weight loss in mouse cachexia models induced by lipopolysaccharide (LPS) administration and by tumor growth are ameliorated by central melanocortin-4 (MC4) receptor (MC4-R) blockade. In contrast to the results seen with MC4 blockade, melanocortin-3 (MC3) receptor knockout (MC3-RKO) mice show illness-induced anorexia and weight loss with LPS administration and with cytokine administration, and they have similar decreases in mobility. Both MC3-RKOs and MC4-RKOs have an intact corticosterone response and fever with LPS injection. In tumor models, we show that MC4-RKO mice resist the loss of LBM brought about by tumor growth, whereas MC3-RKO animals show enhanced tissue wasting. These data underscore the importance of central melanocortin signaling in weight homeostasis and demonstrate differential effects of MC3-R and MC4-R blockade on the development of cachexia.

Original languageEnglish (US)
Pages (from-to)1513-1523
Number of pages11
JournalEndocrinology
Volume144
Issue number4
DOIs
StatePublished - Apr 1 2003

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Melanocortin Receptors
Melanocortins
Cachexia
Lipopolysaccharides
Anorexia
Appetite
Weight Loss
Receptor, Melanocortin, Type 3
Receptor, Melanocortin, Type 4
Basal Metabolism
Neoplasms
Growth
Corticosterone
Starvation
Knockout Mice
Malnutrition
Homeostasis
Chronic Disease
Fever
Fats

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Marks, D., Butler, A. A., Turner, R., Brookhart, G., & Cone, R. D. (2003). Differential role of melanocortin receptor subtypes in cachexia. Endocrinology, 144(4), 1513-1523. https://doi.org/10.1210/en.2002-221099

Differential role of melanocortin receptor subtypes in cachexia. / Marks, Daniel; Butler, Andrew A.; Turner, Renn; Brookhart, Gregor; Cone, Roger D.

In: Endocrinology, Vol. 144, No. 4, 01.04.2003, p. 1513-1523.

Research output: Contribution to journalArticle

Marks, D, Butler, AA, Turner, R, Brookhart, G & Cone, RD 2003, 'Differential role of melanocortin receptor subtypes in cachexia', Endocrinology, vol. 144, no. 4, pp. 1513-1523. https://doi.org/10.1210/en.2002-221099
Marks, Daniel ; Butler, Andrew A. ; Turner, Renn ; Brookhart, Gregor ; Cone, Roger D. / Differential role of melanocortin receptor subtypes in cachexia. In: Endocrinology. 2003 ; Vol. 144, No. 4. pp. 1513-1523.
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