Metabolism of very long-chain monounsaturated fatty acids (22:1) and the adaptation to their presence in the diet.
Unadapted rats and other animal species have a limited capacity to metabolize monounsaturated fatty acids with 22 carbons (22:1). Excess amounts in the diet of fats containing these fatty acids cause a transient accumulation (lipidosis) of triacylglycerol in the heart and other tissues but not in the liver, which seems to export the 22:1 fatty acids as very low density lipoproteins to the blood plasma. The acute lipidosis most probably is explained by a slow oxidation of 22:1 acyl-CoA by the mitochondrial acyl-CoA dehydrogenase combined with an inhibitory effect of this CoA ester on the oxidation of acyl-CoA esters of a more "normal" chain length. Other fatty acid metabolizing enzymes also show slow reaction rates with the 22:1 fatty acids. Upon continued feeding of diets with 22:1 fatty acids, an adaptation takes place and the lipidosis disappears. This adaptation coincides with the development of an increased capacity to chain-shorten the 22:1 fatty acids, especially in the liver, but also in the heart. The chain-shortening seems to be due to a partial beta-oxidation of the 22:1 fatty acids by the peroxisomal beta-oxidation enzyme system which shows an increased activity in adapted rats. In such rats, less 22:1 fatty acids circulate in the plasma very low density lipoproteins than in unadapted rats. The drug clofibrate (ethyl-p-chlorophenoxyisobutyrate) which induces increased activity of the peroxisomal beta-oxidation enzymes, provides partial protection against the lipidosis in unadapted animals. Hydrogenated fish oil (containing different 22:1 isomers and many fatty acids with trans double bonds) is more efficient as an inducer of the chain-shortening of erucic acid in the liver than is rapeseed oil, which contains only one 22:1 fatty acid isomer and no fatty acids with trans double bonds. The hydrogenated fish oil causes less lipidosis than does rapeseed oil when diets containing the same amount of 22:1 fatty acids are fed. It is suggested that CoA esters that are poorly oxidized by the mitochondria (e.g., esters of erucic acid, of some fatty acids with trans double bonds, and of clofibric acid) may trigger the adaptation process.-Bremer, J., and K. R. Norum. Metabolism of very long-chain monounsaturated fatty acids (22:1) and the adaptation to their presence in the diet.
D000214:Acyl Coenzyme A / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D002333:Carnitine Acyltransferases / Q000378:metabolism; D004063:Digestion; D004883:Erucic Acids / Q000378:metabolism* / Q000633:toxicity; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D007408:Intestinal Absorption; D008064:Lipidoses / Q000209:etiology; D008079:Lipoproteins, VLDL / Q000097:blood; D008830:Microbodies / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood
D000214:Acyl Coenzyme A; D004883:Erucic Acids; D005231:Fatty Acids, Unsaturated; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C002232:erucylcarnitine; D002333:Carnitine Acyltransferases; D002331:Carnitine