Anorexia/cachexia of chronic diseases: a role for the TGF‐β family cytokine MIC‐1/GDF15

Journal of Cachexia, Sarcopenia and Muscle

Tsai Vicky W. W.¹  Husaini Yasmin¹  Manandhar Rakesh¹  Lee-Ng K. K. Michelle¹  Zhang Hong Ping¹  Harriott Kate¹  Jiang Lele¹  Lin Shu²  Sainsbury Amanda³  Brown David A.¹ 

[1] St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and UNSW, Sydney, NSW;Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW;The Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney, NSW

关键词: MIC-1/GDF15;    Macrophage inhibitory cytokine 1;    Anorexia;    Cachexia;    TGF-β;    Appetite regulation;   

DOI  :  10.1007/s13539-012-0082-6

来源: Wiley

【 摘 要 】

Abstract

Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least some cancers, the latter process is sometimes driven by marked overexpression of macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15). MIC-1/GDF15 is a transforming growth factor beta (TGF-β) family cytokine that is found in the serum of all normal individuals at an average concentration of about 0.6 ng/ml. Its increased expression in both cancers and other diseases can result in 10–100-fold or more elevation of its serum levels. In experimental animals, serum MIC-1/GDF15 levels at the lower end of this range induce anorexia by direct actions of the circulating cytokine on feeding centres in the brain. Mice with tumours overexpressing MIC-1/GDF15 display decreased food intake, loss of lean and fat mass and cachexia. That this process also mediates anorexia/cachexia in humans is suggested by the fact that there is a direct correlation between the degree of serum MIC-1/GDF15 elevation and the amount of cancer-related weight loss, the first such relationship demonstrated. Further, in experimental animals, weight loss can be reversed by neutralisation of tumour-produced MIC-1/GDF15 with a specific monoclonal antibody, suggesting the possibility of effective therapy of patients with the devastating complication of anorexia/cachexia.

【 授权许可】

CC BY-NC   
© 2012 The Authors. Published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.