Effect of eicosapentaenoic acid, protein and amino acids on protein synthesis and degradation in skeletal muscle of cachectic mice.
Atrophy of skeletal muscle reduces both the quality and quantity of life of patients with cancer cachexia. Loss of muscle mass is thought to arise from a reduction in protein synthesis combined with an enhanced rate of protein degradation, and few treatments are available to counteract this process. Eicosapentaenoic acid (EPA) has been shown to attenuate the enhanced protein degradation, but to have no effect on protein synthesis. This study examines the effect of EPA combined with a protein and amino-acid supplementation on protein synthesis and degradation in gastrocnemius muscle of mice bearing the cachexia-inducing MAC16 tumour. Muscles from cachectic mice showed an 80% reduction in protein synthesis and about a 50-fold increase in protein degradation compared with muscles from nontumour-bearing mice of the same age and weight. Treatment with EPA (1 g kg(-1)) daily reduced protein degradation by 88%, but had no effect on protein synthesis. Combination of EPA with casein (5.35 g kg(-1)) also had no effect on protein synthesis, but when combined with the amino acids leucine, arginine and methionine there was almost a doubling of protein synthesis. The addition of carbohydrate (10.7 g kg(-1)) to stimulate insulin release had no additional effect. The combination involving the amino acids produced almost a doubling of the ratio of protein synthesis to protein degradation in gastrocnemius muscle over that of EPA alone. No treatment had a significant effect on tumour growth rate, but the inclusion of amino acids had a more significant effect on weight loss induced by the MAC16 tumour than that of EPA alone. The results suggest that combination therapy of cancer cachexia involving both inhibition of the enhanced protein degradation and stimulation of the reduced protein synthesis may be more effective than either treatment alone.
Smith
H J
HJ
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.
Greenberg
N A
NA
Tisdale
M J
MJ
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002100:Cachexia / Q000188:drug therapy* / Q000378:metabolism; D002364:Caseins / Q000494:pharmacology*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000150:complications; D014176:Protein Biosynthesis; D015431:Weight Loss / Q000187:drug effects
D000596:Amino Acids; D002364:Caseins; D004338:Drug Combinations; D007328:Insulin; D015118:Eicosapentaenoic Acid