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-6 Desaturase Expression and Its Role in the Polyunsaturated Fatty Acid Inhibition of Fatty Acid Synthase Gene Expression in Mice1
Graduate Program of Nutritional Sciences and the Institute for Cellular and Molecular Biology, The University of Texas, Austin, TX 78712
2To whom correspondence should be addressed.
Dietary polyunsaturated fatty acids (PUFA) of the (n-6) and (n-3)
families uniquely suppress the expression of lipogenic genes while
concomitantly inducing the expression of genes encoding proteins of
fatty acid oxidation. Although considerable progress has been made
toward understanding the nuclear events affected by PUFA, the
intracellular mediator responsible for the regulation of hepatic
lipogenic gene expression remains unclear. On the basis of earlier
fatty acid composition studies, we hypothesized that the 
-6
desaturase pathway was essential for the production of the fatty acid
regulator of gene expression. To address this hypothesis, male BALB/c
mice (n = 8/group) were fed for 5 d a high
glucose, fat-free diet (FF) or the FF plus 50 g/kg 18:2(n-6) with
and without eicosa-5,8,11,14-tetraynoic acid (ETYA) (200 mg/kg diet), a
putative inhibitor of the -6 desaturase pathway. ETYA had no effect
on food intake or weight gain, but it completely prevented 18:2(n-6)
from suppressing the hepatic abundance of fatty acid synthase mRNA.
ETYA ingestion was associated with a decrease in the hepatic content of
20:4(n-6) and an increase in the amount of 18:2(n-6). The fatty acid
composition changes elicited by ETYA were accompanied by a decrease in
the enzymatic activity of -6 desaturase. Interestingly, the hepatic
abundance of -6 desaturase mRNA was actually induced by ETYA one- to
twofold. When the product of -6 desaturase, i.e., 18:3(n-6), was
added to the ETYA plus 18:2(n-6) diet, the hepatic content of 20:4(n-6)
was normalized. In addition, 18:3(n-6) consumption reduced the level of
hepatic -6 desaturase mRNA by 50% and completely prevented the
increase in fatty acid synthase mRNA that was associated with ETYA
ingestion. Apparently, -6 desaturation is an essential step for the
PUFA regulation of the fatty acid synthase gene transcription. Finally,
the suppression of -6 desaturase by PUFA and its induction by ETYA
suggest that the -6 desaturase gene may be regulated by two
different lipid-dependent mechanisms.
KEY WORDS: • -6 desaturase • fatty acid synthase • ETYA • linoleic acid • mice
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