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 f atty acids exert no suppressive action on lipogenic gene expression. T he unique PUFA regulation of gene expression extends beyond the liver to include genes such as adipocyte glucose transporter-4, lymphocyte s tearoyl-CoA desaturase 2, and interleukins. Some of the transcriptiona l effects of PUFA appear to be mediated by eicosanoids, but PUFA suppr ession 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 fa ctor 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 P PAR and n-6 and n-3 PUFA regulation of lipogenic and glycolytic gene t ranscription involve separate and independent mechanisms. Thus PPAR ap pears not to be the PUFA response factor.