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Title:
Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15 | Journal of Cachexia, Sarcopenia and Muscle
Description:
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 10ā100-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.
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Keywords {š}
micgdf, serum, article, google, scholar, pubmed, cas, levels, cancer, anorexiacachexia, cytokine, mice, loss, weight, brown, mass, intake, patients, muscle, food, cachexia, role, macrophage, factor, inhibitory, disease, energy, body, growth, breit, obesity, reduced, appetite, clin, bauskin, data, chronic, normal, direct, regulation, prostate, diseases, tgfβ, superfamily, journal, research, tsai, number, fat, expression,
Topics {āļø}
tgf-beta superfamily cytokine tgf-β superfamily cytokine tumours overexpressing mic-1/gdf15 virus overexpressing mic-1/gdf15 cocaineāamphetamine-related transcript mic-1/gdf15 activated neurons interacting appetite-regulating pathways alpha-melanocyte-stimulating hormone end-stage renal failure growth differentiation factor-15 recombinant mic-1/gdf15 subcutaneously tgf-beta superfamily mic-1/gdf15 tumour expression end-stage renal disease tumour-produced mic-1/gdf15 highest mic-1/gdf15 levels mic-1/gdf15 treated mice mic-1/gdf15-treated mice prospective caseācontrol study nested caseācontrol study elevated serum mic-1/gdf15 serum mic-1/gdf15 levels mic-1/gdf15 serum levels macrophage inhibitory cytokine macrophage inhibitory cytokine-1 anorexia/cachexia mic-1/gdf15 anorexia/cachexia syndrome fall serum mic-1/gdf15 elevation opposing anorexigenic factor important aetiological factor cancer-related weight loss privacy choices/manage cookies growth hormone release mic-1/gdf15 decreased recombinant mic-1/gdf15 elevated serum concentrations local neuronal activation serum mic-1 concentrations receptor knockout models specific monoclonal antibody tumor-induced anorexia eating disorders modify tumour behaviour mic-1/gdf15 administration mic-1/gdf15 utilises tgf-β protein-energy wasting [35] increased serum concentrations regulate food intake regulating food intake
Questions {ā}
- 3 Does MIC-1/GDF15 play a role in physiological appetite regulation?
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headline:Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15
description: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 0.6Ā ng/ml. Its increased expression in both cancers and other diseases can result in 10ā100-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.
datePublished:2012-08-31T00:00:00Z
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MIC-1/GDF15
Macrophage inhibitory cytokine 1
Anorexia
Cachexia
TGF-β
Appetite regulation
Internal Medicine
Oncology
Geriatrics/Gerontology
Clinical Nutrition
Molecular Medicine
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headline:Anorexia/cachexia of chronic diseases: a role for the TGF-β family cytokine MIC-1/GDF15
description: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 0.6Ā ng/ml. Its increased expression in both cancers and other diseases can result in 10ā100-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.
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MIC-1/GDF15
Macrophage inhibitory cytokine 1
Anorexia
Cachexia
TGF-β
Appetite regulation
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Oncology
Geriatrics/Gerontology
Clinical Nutrition
Molecular Medicine
Pharmacology/Toxicology
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