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.