title: Anorexia-cachexia and obesity treatment may be two sides of the same coin: role of the TGF-b superfamily cytokine MIC-1/GDF15.
abstract: Anorexia-cachexia associated with cancer and other diseases is a common and often fatal condition representing a large area of unmet medical need. It occurs most commonly in advanced cancer and is probably a consequence of molecules released by tumour cells, or tumour-associated interstitial or immune cells. These may then act directly on muscle to cause atrophy and/or may cause anorexia, which then leads to loss of both fat and lean mass. Although the aetiological triggers for this syndrome are not well characterized, recent data suggest that MIC-1/GDF15, a transforming growth factor-beta superfamily cytokine produced in large amounts by cancer cells and as a part of other disease processes, may be an important trigger. This cytokine acts on feeding centres in the hypothalamus and brainstem to cause anorexia leading to loss of lean and fat mass and eventually cachexia. In animal studies, the circulating concentrations of MIC-1/GDF15 required to cause this syndrome are similar to those seen in patients with advanced cancer, and at least some epidemiological studies support an association between MIC-1/GDF15 serum levels and measures of nutrition. This article will discuss its mechanisms of central appetite regulation, and the available data linking this action to anorexia-cachexia syndromes that suggest it is a potential target for therapy of cancer anorexia-cachexia and conversely may also be useful for the treatment of severe obesity.
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia.|Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: V W W
authors.initials: VW
authors.lastname: Tsai
authors.affiliation: The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia.|Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: D A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: A
authors.identifier: http://orcid.org/0000-0001-9176-1574
authors.initials: A
authors.lastname: Salis
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital Sydney, Sydney, New South Wales, Australia.|Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: S N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology* / Q000523:psychology / Q000628:therapy; D001066:Appetite / Q000187:drug effects / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002100:Cachexia / Q000209:etiology* / Q000523:psychology / Q000628:therapy; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055436:Growth Differentiation Factor 15 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends; D009369:Neoplasms / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1