TRANSCRIPTIONAL CONTROL OF THE STEAROYL-COA DESATURASE-1 GENE BY POLYUNSATURATED FATTY-ACIDS

The effect of exogenous fatty acids on expression of the stearoyl-CoA destaurase-1 (SCD1) gene was assessed both in vivo and ex vivo. Mice f ed a fat-free diet or a diet containing a largely monounsaturated (18: 1) fat, i.e.,olive oil, expressed high levels of hepatic SCD1 mRNA. In contrast, in mice fed diets containing primarily polyunsaturated (18: 2 and 18:3) fats, expression of the hepatic SCD1 message was markedly suppressed. Similar experiments with pure fatty acid esters showed tha t arachidonate (20:4) and linoleate (18:2) were far more potent in dow n-regulating expression of the hepatic SCD1 message than oleate (18:1) , an end-product (as its CoA thioester) of the SCD1-catalyzed reaction . The reduction of hepatic SCD1 mRNA appears to be primarily due to in hibition of SCD1 gene transcription since polyunsaturated fatty acids caused a decrease in run-on transcription of the gene comparable to th e decrease in message level. Consistent with the effects observed in v ivo, unsaturated fatty acids suppressed the expression of SCD1 mRNA by rat hepatocytes cultured in serum-free medium. Suppression increased with degree of unsaturation with arachidonic (20:4) and eicosapentaeno ic (20:5) acids,causing a greater than or equal to 90% reduction in th e level of SCD1 message. Thus, the SCD1 gene, like the fatty acid synt hase and S14 genes, undergoes coordinate transcriptional down-regulati on in response to unsaturated fatty acids. (C) 1994 Academic Press, In c.