Protein sparing in skeletal muscle during prolonged starvation. Dependence on lipid fuel availability.
Previous studies indicated that protein sparing in skeletal muscle during prolonged starvation depends on the availability of lipid fuels. To test this relationship further, fasted rats conserving protein were treated in vivo for 6-8 h with the antilipolytic agent nicotinic acid (NA) or with tetradecylglycidate (TDGD), an inhibitor of long-chain fatty acid oxidation. After treatment, protein synthesis and degradation in skeletal muscle were evaluated with the perfused rat hindquarter. NA treatment decreased plasma 3-hydroxybutyrate and free fatty acids and increased plasma urea and urine urea excretion, indicating increased breakdown of body protein. TDGD produced similar metabolic effects, except that plasma free fatty acids were markedly increased as a result of inhibition of fatty acid oxidation. NA and TDGD also decreased plasma insulin and increased plasma corticosteroid. Inhibition of lipid metabolism in vivo resulted in accelerated loss of protein from skeletal muscle due to decreased protein synthesis and increased protein breakdown. NA increased both total (i.e., tyrosine release) and myofibrillar (i.e., 3-methylhistidine release) protein breakdown, whereas TDGD increased the breakdown of only nonmyofibrillar proteins (i.e., 3-methylhistidine release by perfused hindquarter was not altered). These data indicate that lipid fuels may directly modulate protein metabolism in muscle during prolonged starvation and may prevent a rise in catabolic hormones. They also indicate that free fatty acids may directly attenuate the breakdown of myofibrillar proteins in muscle during prolonged starvation and that this may be unrelated to their oxidation.
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001806:Blood Urea Nitrogen; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000378:metabolism*; D013864:Thioglycolates / Q000494:pharmacology
D004852:Epoxy Compounds; D005227:Fatty Acids; D006885:Hydroxybutyrates; D009124:Muscle Proteins; D013864:Thioglycolates; D009525:Niacin; C017487:2-mercaptoacetate; C021756:2-tetradecylglycidic acid; D020155:3-Hydroxybutyric Acid