Inflammatory burden and amino acid metabolism in cancer cachexia.
OBJECTIVE
Cancer cachexia is associated with marked alterations in skeletal muscle protein metabolism that lead to muscle wasting and, in some cases, death. The inflammatory response elicited by cancer is a likely, if not primary, mediator of these alterations. This review focuses on the possible relationship between inflammatory signaling and altered amino acid metabolism in cancer.


RESULTS
Loss of skeletal muscle in cancer patients can potentially be due to anorexia and early satiety, reduced muscle protein synthesis, and/or increased muscle protein breakdown. Inflammation has been associated with each of these mechanisms. Effects on appetite appear to be mediated by the melanocortin system in the hypothalamus. Studies in animal models of cachexia suggest that modulation of orexigenic and anorexigenic pathways in this system may improve nutrient consumption. Inflammatory cytokines such as IL-6 and TNF-alpha are likely to contribute to the effects of inflammation on muscle protein metabolism through several pathways.


CONCLUSIONS
Limited studies in humans suggest that targeted anti-inflammatory and nutritional interventions may ameliorate the net catabolic effect on skeletal muscle protein metabolism. Future studies of the precise mechanism of muscle protein loss, as well as novel or combination therapies to inhibit inflammation and promote anabolism, are warranted.
Durham
William J
WJ
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Dillon
Edgar Lichar
EL
Sheffield-Moore
Melinda
M
D000596:Amino Acids / Q000378:metabolism* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D002100:Cachexia / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000150:complications*; D007328:Insulin / Q000627:therapeutic use; D009124:Muscle Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000150:complications*; D013739:Testosterone / Q000627:therapeutic use
D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D007328:Insulin; D009124:Muscle Proteins; D013739:Testosterone