Peripheral mechanisms involved with catabolism

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Abstract
This review summarizes recent developments concerning the mechanisms of skeletal muscle and adipose tissue breakdown, which are a hallmark of cachexia during many diseases. Current knowledge on the hypermetabolism which often contributes to cachexia is also considered. Recent studies have identified interactions between Ca2+, proinflammatory cytokines (in particular tumor necrosis factor-α) and the activation of transcription factors (e.g. nuclear factor-κB) in the stimulation of major proteolytic pathways in cachexia. Progress has also been made in explaining the inhibiting effects of several drugs on protein breakdown. Advances in our understanding of the mechanisms of adipose tissue catabolism in cachexia include demonstrations that (1) tumor necrosis factor-α, in addition to its direct lipolytic effect, promotes adipose tissue breakdown by inhibiting adipocyte differentiation and increasing adipocyte apoptosis, (2) interleukin-6 has a lipolytic effect, and (3) chemokines are expressed by adipocytes and interact with tumor necrosis factor-α to cause lipolysis. Concerning the hypermetabolism in cachexia, new evidence supports previous theories that uncoupling protein-2 and 3 are primarily involved in the generation of reactive oxygen species and in the control of fatty acid flux across the mitochondrial membrane, respectively. Furthermore, the cytokine-induced transcriptional coactivator-1 for the peroxysome proliferator-activated receptor-gamma was recently identified as a contributor to hypermetabolism. These new insights into major catabolic pathways during cachexia provide a focus for future studies in this area and may help to develop promising therapeutic approaches.