| Abstrakt: |
Cachexia is brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. This combination is found in a number of disorders including cancer, chronic kidney disease (CKD), AIDS, cystic fibrosis, chronic heart failure, rheumatoid arthritis, and Alzheimer's disease. Cachexia has a stronger correlation with survival than any other current measure of diseases such as AIDS, cancer, and CKD. The underlying mechanism of increased resting metabolic rate may involve the increased activity of mitochondrial uncoupling proteins. Chronic overproduction of cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, may lead to cachexia in various chronic illness models, through the nuclear factor-KB and ATP-ubiquitin-dependent proteolytic pathways. Inhibition of these cytokines in experimental models ameliorated cachexia. Cytokines may also act on the central nervous system to alter the release and function of neuropeptides and melanocortin receptors in the hypothalamus, thereby altering both appetite and metabolic rate. Further research into the molecular pathways leading to cachexia may lead to novel therapeutic therapy for this devastating and potentially fatal complication of chronic disease. [ABSTRACT FROM AUTHOR] |
