POLYUNSATURATED FATTY ACID-MEDIATED SUPPRESSION OF INSULIN-DEPENDENT GENE-EXPRESSION OF LIPOGENIC ENZYMES IN RAT-LIVER

The effects of dietary polyunsaturated fat on insulin-dependent gene e xpression of lipogenic enzymes and a possible mechanism for PUFA-media ted suppression of the gene expression have been investigated in rat l ivers. When diabetic rats were injected with insulin, the insulin dose -dependent induction of lipogenic enzyme mRNAs were markedly reduced w ith increasing dietary corn oil. On the other hand, the PUFA-mediated suppression of the mRNA concentrations was partially restored by treat ment with pioglitazone, a candidate for increasing insulin receptor ph osphorylation. Moreover, insulin binding to receptors of liver, recept or autophosphorylation, and kinase activity toward exogenous substrate were lower in the corn oil diet group than in the hydrogenated fat gr oup. The PUFA-mediated suppression of insulin binding was somewhat res tored by pioglitazone, and the suppression of insulin receptor phospho rylation was significantly restored. It is suggested that the PUFA-med iated suppression of insulin-dependent gene expression of lipogenic en zymes can be ascribed to a decrease in insulin receptor binding primar ily and also to receptor phosphorylation. Thus, PUFA appears to suppre ss the lipogenic enzyme gene expression stimulated by insulin.