Polyunsaturated fatty acid regulation of hepatic gene transcription

Polyunsaturated fatty acids (PUFA) of the n-6 and n-3 families inhibit transcription of a number of hepatic lipogenic and glycolytic genes, e.g. fatty acid synthase. In contrast, saturated and monounsaturated fatty acids exert no suppressive action on lipogenic gene expression. The unique PUFA regulation of gene expression extends beyond the liver to include genes such as adipocyte glucose transporter-4, lymphocyte stearoyl-CoA desaturase 2, and interleukins. Some of the transcriptional effects of PUFA appear to be mediated by eicosanoids, but PUFA suppression of lipogenic and glycolytic genes is independent of eicosanoid synthesis and appears to involve a nuclear mechanism directly modified by PUFA. With the recent cloning of a fatty acid-activated nuclear factor termed peroxisome-proliferator-activated receptor (PPAR) has come the suggestion that PPAR may be the PUFA response factor. This review, however, presents several lines of evidence that indicate that the PPAR and n-6 and n-3 PUFA regulation of lipogenic and glycolytic gene transcription involve separate and independent mechanisms. Thus PPAR appears not to be the PUFA response factor.