POLYUNSATURATED FATTY-ACID REGULATION OF LIPOGENIC ENZYME GENE-EXPRESSION IN LIVER OF GENETICALLY-OBESE RAT

The polyunsaturated fatty acid regulation of lipogenic enzyme gene exp ression in genetically obese rats (Wistar fatty, non-insulin-dependent diabetes mellitus) has been investigated. The hepatic mRNA concentrat ions and activities of lipogenic enzymes in the fatty and lean rat wer e greatly increased by feeding a hydrogenated fat diet to fasted rats, and also reached similar maximum levels with similar time courses. By feeding a corn oil diet, however, the increases were markedly reduced in the lean rats, but were not significantly reduced in the fatty rat s. Consequently, when the animals were fed corn oil, the mRNA concentr ations and activities in the fatty rats were higher than those in the lean. Thus, it appeared that the higher gene expression in the fatty r ats can be ascribed to the defects of polyunsaturated fatty acid suppr ession. On the other hand, insulin binding to receptors in the liver w as reduced by the corn oil diet in the lean rats but was not reduced i n the fatty rats (although the insulin binding level was lower in the Wistar fatty rats than in the lean). Changes in the insulin receptor a utophosphorylation and kinase activity toward exogenous substrate were similar to the insulin binding. It is suggested that the polyunsatura ted fatty acids may not suppress insulin binding activity to receptors in the livers of the fatty rats, probably due to down regulation by h yperinsulinemia. The defects of polyunsaturated fatty acid suppression of lipogenic enzyme gene expression may be one of the factors of obes ity.