Abstract. cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the c26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mrnA of atrogin and murf). Male cD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; tB) or were sham injected (control; c). they were fed standard diets or diets supplemented with leucine [1 gr (tB1leu) or 8 gr (tB8leu) supplemented leucine per kg feed]; tB and c received 8.7% leu/g protein, tB1leu received 9.6% leu/g protein and tB8leu received 14.6 leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mg), tibialis anterior (mtA), extensor digitorum longus (meDl) and soleus (ms) muscles. In tumor-bearing (tB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mrnA in the meDl increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to tB, the mass of the mg was +23% in tB8leu, and +22% in mtA (p<0.05). However, leucine supplementation did not change atrogin and murf mrnA levels. total plasma amino acid concentrations increased in tB, especially for taurine, lysine, arginine and alanine (p<0.05). leucine supplementation attenuated the increase in total plasma amino-acid concentrations (p<0.05). Irrespective of changes in muscle protein breakdown markers, leucine supplementation reduced muscle wasting in tumor-bearing cachectic mice and attenuated changes in plasma amino acids.
Introductioncancer cachexia is characterized by a progressive loss of fat mass and skeletal muscle mass. Because it results from systemic inflammation induced by the tumor (1-3), the metabolic changes it causes are different from those of starvation (4). the skeletal muscle wasting that accompanies cancer cachexia is associated with increased morbidity and mortality (4,5); its severity is inversely related to the length of time a patient survives (6).the skeletal muscle protein balance depends on the sum of protein synthesis and breakdown. reportedly, protein synthesis is stimulated and protein breakdown is inhibited by the essential amino acid, leucine (7-10). In weight-losing cachectic cancer patients, the cause of muscle wasting is a decrease skeletal muscle-protein synthesis (11) or a lack to increase skeletal muscle-protein synthesis to counter-balance an increase in protein degradation (12). net muscle-protein synthesis in these patients might thus be stimulated by a nutritional intervention with leucine, such as that used in Abbreviations: BcAA, branched-chain amino acids; Bw, body weight; c, sham-injected control mice; cHs, contact hypersensitivity test; cw, carcass weight; gApDH, lyceraldehyde-3-phosphate dehydrogenase; HBss, Ha...
