title: Cachexia in chronic kidney disease: role of inflammation and neuropeptide signaling.
abstract: OBJECTIVE
  This review will update clinicians and basic scientists who are interested in the clinical relevance and molecular mechanism of uremic cachexia. Recent studies that examine the role of cytokines and hypothalamic neuropeptides are emphasized.
  
  
  RESULTS
  A current hypothesis of the cause of cachexia in chronic illness is that proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and leptin, act on the central nervous system to alter the release and function of several key neurotransmitters, thereby altering both appetite and metabolic rate. Proinflammatory cytokines also activate the transcription factor nuclear factor-kappaB, resulting in decreased protein synthesis, and activate the ubiquitin-mediated proteolytic system, which is the major system involved in increased protein degradation.
  
  
  CONCLUSIONS
  This review highlights the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and the potential of peripheral administration of melanocortin-4 receptor antagonists as a novel therapeutic approach.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA. makr@ohsu.edu
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mak
authors.forename: Wai
authors.initials: W
authors.lastname: Cheung
mesh_terms: D000855:Anorexia / Q000503:physiopathology; D002100:Cachexia / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D004734:Energy Metabolism; D006801:Humans; D034141:Hypoalbuminemia / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D007674:Kidney Diseases / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology; D009479:Neuropeptides / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D009479:Neuropeptides