Polyunsaturated fatty acid regulation of hepatic gene transcription

Polyunsaturated fatty acids (PUFA) modulate the rate of gene transcription for a number of different genes including hepatic lipogenic and glycolytic genes, adipose Glut-4 and stearoyl-CoA desaturase and interleukins. Some of the transcriptional effects of PUFA appear to be mediated by eicosanoids, but the 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-acitivated receptor (PPAR) has come the suggestion that PPAR may be the PUFA response factor. However, this review presents several lines of evidence that indicate that the PPAR and PUFA regulation of gene transcription involves separate and independent mechanisms, and the PPAR is not the PUFA response factor.