Inhibitory Effects of Exogenous Polyunsaturated Fatty Acids on Lipogenic Enzymes in Rat Liver
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Inhibitory effects of exogenous polyunsaturated fatty acids were investigated on the enzymes, which catalyze fatty acid synthesis, <I>in vivo</I> and <I>in vitro</I>.<BR>In response to refeeding of a high-carbohydrate, fat-free diet, a striking adaptive rise in the activities of lipogenic enzymes of rat liver was associated with concomitant deficiency in essential fatty acids in both phospholipid and FFA fractions of the liver lipids. Oral administration of methylesters of polyunsaturated fatty acids recovered the supranormal activities of lipogenic enzymes toward the normal. The degree of fall in enzyme activity was a function of the dose of polyunsaturated fatty acids administered and the length of experimental periods. Moreover, dampening of the enzyme activity was closely related to exogenous input of polyunsaturated fatty acids in the liver.<BR>Fatty acid composition of liver FFA was disclosed to be distinct from that of plasma FFA in starved rats. Total FFA concentration in the whole liver was assumed to be approximately 6×10<SUP>-4</SUP>M. Most of FFA (84 %), however, was bouud to liver cell particulates.<BR>Examination of lipogenic enzymes <I>in vitro</I> revealed that free fatty acids inhibited enzyme activity and that polyunsaturated fatty acids were more potent than saturated or monounsaturated fatty acids with the exception of ω 7 monoenic acids.<BR><I>In vitro</I> concentration of arachidonic acid required for 50% inhibition of acetyl CoA carboxylase activity was found to be 7×10<SUP>-5</SUP>M, which was much higher than the maximum concentration of free arachidonic acid in liver supernatant. Furthermore, <I>in vitro</I> inhibitions of both fatty acid synthetase and malic enzyme activity by polyunsaturated fatty acids were less evident.<BR>These results strongly suggest that exogenous polyunsaturated fatty acids may dampen the activity of the lipogenic enzyme set in its synthetic site as alsoreported by Majerus and Kilburn (9).
- Japan Society of Clinical Chemistryの論文
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