Cachexia: lessons from melanocortin antagonism.
It is well established that disruptions in melanocortin signaling in the CNS result in morbid obesity, but only recently has evidence linked the activation of this system with the production of cachexia, also known as disease-associated wasting. Pro-opiomelanocortin-producing neurons, which express cytokine receptors, show increased activation in the presence of several cytokines that are increased in diseases that are associated with cachexia. Recent experiments show that blockade of melanocortin signaling using antagonists to the melanocortin MC(4) receptor attenuates disease-associated anorexia and wasting in rodent models of cancer and renal failure. This successful inhibition of cachexia is important because loss of appetite and lean body mass worsen the prognosis of many the diseases with which cachexia is associated.
Deboer
Mark D
MD
Department of Pediatrics, Oregon Health and Science University, 707 SW Gaines Rd., Portland, Oregon 97239, USA. marksd@ohsu.edu
Marks
Daniel L
DL
D054369:Agouti-Related Protein; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002100:Cachexia / Q000188:drug therapy* / Q000517:prevention & control; D004435:Eating; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors*
D054369:Agouti-Related Protein; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D044101:Receptors, Melanocortin; D011333:Pro-Opiomelanocortin