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.