Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15
| Autor: | Shu Lin, Kate Harriott, Rakesh Manandhar, Hong Ping Zhang, Samuel N. Breit, K. K. Michelle Lee-Ng, Lele Jiang, Yasmin Husaini, Vicky Wang-Wei Tsai, Amanda Sainsbury, David Brown |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
TGF-β
medicine.medical_specialty Cachexia medicine.medical_treatment Review Clinical nutrition Anorexia Macrophage inhibitory cytokine 1 Weight loss Physiology (medical) Internal medicine Appetite regulation medicine Orthopedics and Sports Medicine biology business.industry digestive oral and skin physiology MIC-1/GDF15 Macrophage inhibitory cytokine 1 Anorexia Cachexia TGF-β Appetite regulation Transforming growth factor beta medicine.disease Endocrinology Cytokine Immunology biology.protein GDF15 medicine.symptom MIC-1/GDF15 business Transforming growth factor |
| Zdroj: | Journal of Cachexia, Sarcopenia and Muscle |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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