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. © 2004 Cancer Research UK.

Publication DOI: https://doi.org/10.1038/sj.bjc.6601981
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
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Uncontrolled Keywords: protein synthesis,protein degradation,muscle,cachexia,Cancer Research,Oncology
Publication ISSN: 1532-1827
Last Modified: 20 Feb 2024 08:06
Date Deposited: 19 Aug 2019 08:50
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.natu ... s/6601981a.html (Publisher URL)
PURE Output Type: Article
Published Date: 2004-07-19
Authors: Smith, Helen J.
Greenberg, N.A.
Tisdale, Michael J.

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