Polyunsaturated Fatty Acid-Mediated Suppression of Insulin-Dependent Gene Expression of Lipogenic Enzymes in Rat Liver.

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The effects of dietary polyunsaturated fat on insulin-dependent gene expression of lipogenic enzymes and a possible mechanism for PUFA-mediated suppression of the gene expression have been in-vestigated in rat livers. When diabetic rats were injected with insulin, the insulin dose-dependent induction of lipogenic enzyme mRNAs were markedly reduced with increasing dietary corn oil. On the other hand, the PUFA-mediated suppression of the mRNA concentrations was partially restored by treatment with pioglitazone, a candidate for increasing insulin receptor phosphorylation. Moreover, insulin binding to receptors of liver, receptor autophosphorylation, and kinase activity toward exogenous sub-strate were lower in the corn oil diet group than in the hydrogenated fat group. The PUFA-mediated suppression of insulin binding was some-what restored by pioglitazone, and the suppression of insulin receptor phosphorylation was significantly restored. It is suggested that the PUFA-mediated suppression of insulin-dependent gene expression of lip-ogenic enzymes can be ascribed to a decrease in insulin receptor binding primarily and also to receptor phosphorylation. Thus, PUFA appears to suppress the lipogenic enzyme gene expression stimulated by insulin.
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