Muscle wasting and protein metabolism

ABSTRACT Accelerated muscle proteolysis is the primary cause of muscle wasting in many catabolic diseases such as diabetes mellitus, renal and liver failure, HIV infection and AIDS, and cancer. In individuals with catabolic diseases, as is the case with fasting states (anorexia and starvation), protein breakdown increases while protein synthesis declines, resulting in negative muscle protein balance. The pathway responsible for accelerated proteolysis in catabolic conditions is the ubiquitin-proteosome-dependent system. Muscle proteolysis increases under conditions of acidosis, up-regulation of branched-chain ketoacid dehydrogenase, the presence of catabolic hormones (glucocorticoids, thyrotoxic states), insulin resistance, and multiple cytokines (interleukin-1 and -6 and tumor necrosis factor). In contrast, factors that suppress muscle proteolysis and wasting, leading to a state of adaptation, include dietary protein deficiency with adequate energy intake, use of anabolic agents, and resistance exercise training. The understanding of the biochemical adaptations that reduce protein degradation and improve nitrogen balance are important for the development of effective therapies to combat muscle wasting and improve protein homeostasis with catabolic illnesses.

Implications

The balance between muscle protein synthesis and degradation determines muscle mass and function. Understanding the role of mediators of muscle wasting on nutritional and metabolic end points of protein homeostasis is critical to reducing morbidity and mortality associated with chronic diseases and to developing appropriate interventions. There is considerable interest in modulating protein metabolism with hormones and(or) resistance training in several protein-wasting conditions. Further research is needed to elucidate the molecular and cellular mechanisms that contribute to the maintenance of muscle mass, to understand the responsiveness of muscle to different treatment interventions, and to determine possible interactions between treatment modalities. In addition, catabolic response may differ by disease condition, such that some interventions tested in a group of patients may not necessarily be safe and effective in another group.

Key Words: Protein Turnover, Muscle Wasting, Nutritional Status, Chronic Infections

Ö2002 American Society of Animal Science. All rights reserved.
J. Anim. Sci. 80(E. Suppl. 2):E98-E105