title: Cachexia and obesity: two sides of one coin?
abstract: OBJECTIVE
  Leptin, a member of the interleukin-6 superfamily of proteins, modifies the gene expression and synthetic pathway of both orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) molecules in the hypothalamus, thereby controlling adipocyte energy stores. Lack of leptin secretion or the inability of leptin to interact with these molecules via leptin receptors, prevent leptin's effects and lead to obesity. It is not well known, however, how these feeding-regulatory molecules are affected in cachexia associated with cancer and other critical conditions in which cytokines such as interleukin-1 and interleukin-6 may have a key role.
  
  
  RESULTS
  Decreased leptin and increased leptin-like signaling by cytokines in the hypothalamus are the hallmark of obesity and cachexia, respectively. Increased orexigenic and impaired anorexigenic signaling produces hyperphagia and obesity, while the reverse applies to anorexia-cachexia in which adaptive feeding response to starvation is lacking or insufficient.
  
  
  CONCLUSIONS
  Imbalanced operation of orexigenic and anorexigenic circuits perturbs the homeostatic loop of body weight regulation leading to either obesity or cachexia. Modifiers of the central effects on appetite and energy metabolism could restore the balance and be effective for treating both conditions. In cachexia this may especially be true when combined with agents that target muscle and protein breakdown.
authors.affiliation: Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. inui@med.kobe-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Inui
authors.forename: Michael M
authors.initials: MM
authors.lastname: Meguid
mesh_terms: D000855:Anorexia / Q000378:metabolism; D001835:Body Weight / Q000502:physiology*; D002100:Cachexia / Q000378:metabolism* / Q000628:therapy; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000628:therapy
chemical_list: D020738:Leptin