title: Exploiting the therapeutic potential of leptin signaling in cachexia.
abstract: OBJECTIVE
  The anorexia-cachexia syndrome is a complication of many chronic conditions including cancer, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease (CKD). Leptin levels are significantly elevated in CKD patients and are associated with markers of poor nutritional status as well as mortality and morbidity. This review will focus on the mechanism and exploit the therapeutic potential of leptin signaling in CKD-associated cachexia.
  
  
  RESULTS
  Studies in db/db mice show that the lack of leptin receptor is protective against CKD-induced cachexia. Blockade of leptin's downstream mediators, such as melanocortin-4 receptor, attenuated CKD-associated cachexia. Pegylation of leptin antagonists resulted in a potent and effective long-acting reagents suitable for in-vivo studies or therapies. Pegylated leptin antagonist treatment ameliorates CKD-associated cachexia in mice.
  
  
  CONCLUSIONS
  Leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.
authors.affiliation: aDivision of Pediatric Nephrology, Rady Children's Hospital San Diego, University of California San Diego, La Jolla, California, USA bInstitute of Biochemistry, Food Science and Nutrition, Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mak
authors.forename: Wai W
authors.initials: WW
authors.lastname: Cheung
authors.forename: Arieh
authors.initials: A
authors.lastname: Gertler
mesh_terms: D000818:Animals; D002100:Cachexia / Q000188:drug therapy* / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors*; D051379:Mice; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D020738:Leptin; D044105:Receptor, Melanocortin, Type 4; D054411:Receptors, Leptin