This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marks, D. L. Articles by Cone, R. D. Search for Related Content PubMed PubMed Citation Articles by Marks, D. L. Articles by Cone, R. D.

Differential Role of Melanocortin Receptor Subtypes in Cachexia

Department of Pediatric Endocrinology (D.L.M., G.B.), Veterans Affairs Medical Center (R.T.), Vollum Institute (R.D.C.), Oregon Health and Science University, Portland, Oregon 97201; and Pennington Institute (A.A.B.), Baton Rouge, Louisiana 70808

Address all correspondence and requests for reprints to: Roger D. Cone, Vollum Institute Mailcode L474, Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97201. E-mail: cone{at}ohsu.edu.

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.

This article has been cited by other articles:

				A. Laviano, A. Inui, D. L. Marks, M. M. Meguid, C. Pichard, F. Rossi Fanelli, and M. Seelaender Neural control of the anorexia-cachexia syndrome Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1000 - E1008. [Abstract] [Full Text] [PDF]

				J. L. Sartin, D. L. Marks, C. D. McMahon, J. A. Daniel, P. Levasseur, C. G. Wagner, B. K. Whitlock, and B. P. Steele Central role of the melanocortin-4 receptors in appetite regulation after endotoxin J Anim Sci, October 1, 2008; 86(10): 2557 - 2567. [Abstract] [Full Text] [PDF]

				E. R. Ropelle, J. R. Pauli, K. G. Zecchin, M. Ueno, C. T. de Souza, J. Morari, M. C. Faria, L. A. Velloso, M. J. A. Saad, and J. B. C. Carvalheira A Central Role for Neuronal Adenosine 5'-Monophosphate-Activated Protein Kinase in Cancer-Induced Anorexia Endocrinology, November 1, 2007; 148(11): 5220 - 5229. [Abstract] [Full Text] [PDF]

				H. Shimizu, K. Inoue, and M. Mori The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure J. Endocrinol., April 1, 2007; 193(1): 1 - 9. [Abstract] [Full Text] [PDF]

				R. D. Cone Studies on the Physiological Functions of the Melanocortin System Endocr. Rev., December 1, 2006; 27(7): 736 - 749. [Abstract] [Full Text] [PDF]

				J. R. Nicholson, G. Kohler, F. Schaerer, C. Senn, P. Weyermann, and K. G. Hofbauer Peripheral Administration of a Melanocortin 4-Receptor Inverse Agonist Prevents Loss of Lean Body Mass in Tumor-Bearing Mice J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 771 - 777. [Abstract] [Full Text] [PDF]

				N. R. Vulliemoz, E. Xiao, L. Xia-Zhang, M. Ferin, and S. L. Wardlaw Melanocortin Modulation of Inflammatory Cytokine and Neuroendocrine Responses to Endotoxin in the Monkey Endocrinology, April 1, 2006; 147(4): 1878 - 1883. [Abstract] [Full Text] [PDF]

				L. S. Tallam, D. E. Stec, M. A. Willis, A. A. da Silva, and J. E. Hall Melanocortin-4 Receptor-Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia Hypertension, August 1, 2005; 46(2): 326 - 332. [Abstract] [Full Text] [PDF]

				S. Markison, A. C. Foster, C. Chen, G. B. Brookhart, A. Hesse, S. R. J. Hoare, B. A. Fleck, B. T. Brown, and D. L. Marks The Regulation of Feeding and Metabolic Rate and the Prevention of Murine Cancer Cachexia with a Small-Molecule Melanocortin-4 Receptor Antagonist Endocrinology, June 1, 2005; 146(6): 2766 - 2773. [Abstract] [Full Text] [PDF]

				K. A. Takahashi, J. L. Smart, H. Liu, and R. D. Cone The Anorexigenic Fatty Acid Synthase Inhibitor, C75, Is a Nonspecific Neuronal Activator Endocrinology, January 1, 2004; 145(1): 184 - 193. [Abstract] [Full Text] [PDF]

				G. Li, C. V. Mobbs, and P. J. Scarpace Central Pro-opiomelanocortin Gene Delivery Results in Hypophagia, Reduced Visceral Adiposity, and Improved Insulin Sensitivity in Genetically Obese Zucker Rats Diabetes, August 1, 2003; 52(8): 1951 - 1957. [Abstract] [Full Text] [PDF]