Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia.
Depletion of muscle and adipose tissue in cancer cachexia appears to arise not only from decreased food intake but also from the production of catabolic factors by certain tumours. Experiments with the cachexia-inducing MAC16 tumour in mice showed that when part of the carbohydrate calories were replaced by fish oil, host body weight loss was inhibited. The effect occurred without an alteration of either the total calorie consumption or nitrogen intake. Instead, one of the polyunsaturated fatty acids (PUFA) in fish oil, eicosapentaenoic acid (EPA), was found directly to inhibit tumour-induced lipolysis. The effect was structurally specific, as two related PUFA, docosahexaenoic acid (DHA) and gamma-linolenic acid (GLA), were without effect. The antilipolytic effect of EPA arose from an inhibition of the elevation of cyclic AMP in adipocytes in response to the lipid mobilizing factor. The increased protein degradation in the skeletal muscle of cachectic animals was also inhibited by EPA. This effect was due to the inhibition of the rise in muscle prostaglandin E2 in response to a tumour-produced proteolytic factor by EPA. Thus, reversal of cachexia by EPA in this mouse model results from its capacity to interfere with tumour-produced catabolic factors. Similar factors have been detected in human cancer cachexia.
Tisdale
M J
MJ
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
D000230:Adenocarcinoma / Q000150:complications*; D000818:Animals; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000150:complications*; D015232:Dinoprostone / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005395:Fish Oils / Q000627:therapeutic use; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D005395:Fish Oils; D009124:Muscle Proteins; D015118:Eicosapentaenoic Acid; D015232:Dinoprostone