J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M600273-JLR200 on September 27, 2006

Papers In Press, published online ahead of print December 1, 2006
J. Lipid Res., doi:10.1194/jlr.M600273-JLR200
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Journal of Lipid Research, Vol. 47, 2712-2717, December 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Trans geometric isomers of EPA decrease LXR{alpha}-induced cellular triacylglycerol via suppression of SREBP-1c and PGC-1ß

Nobuhiro Zaima, Tatsuya Sugawara, Dai Goto and Takashi Hirata1

Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan

Published, JLR Papers in Press, September 27, 2006.

1 To whom correspondence should be addressed. e-mail: hiratan{at}kais.kyoto-u.ac.jp

Dietary mono- or di-trans fatty acids with chain lengths of 18–22 increase the risk of cardiovascular diseases because they increase LDL cholesterol and decrease HDL cholesterol in the plasma. However, the effects of trans isomers of PUFAs on lipid metabolism remain unknown. Dietary PUFAs, especially eicosapentaenoic acid (EPA) in marine oils, improve serum lipid profiles by suppressing liver X receptor {alpha} (LXR{alpha}) activity in the liver. In this study, we compared the effects of trans geometric isomers of eicosapentaenoic acid (TEPA) on triacylglycerol synthesis induced by a synthetic LXR{alpha} agonist (T0901317) with the effects of EPA in HepG2 cells. TEPA significantly decreased the amount of cellular triacylglycerol and the expression of mRNAs encoding fatty acid synthase, stearoyl-CoA desaturase-1, and glycerol-3-phosphate acyltransferase induced by T0901317 compared with EPA. However, there was no significant difference between the suppressive effect of TEPA or EPA on the expression of sterol-regulatory element binding protein-1c (SREBP-1c) induced by T0901317. We found that TEPA, but not EPA, decreased the mRNA expression of peroxisome proliferator-activated receptor {gamma} coactivator 1ß (PGC-1ß), which is a coactivator of both LXR{alpha} and SREBP-1. These results suggest that the hypolipidemic effect of TEPA can be attributed to a decrease not only in SREBP-1 but also in PGC-1ß expression.

Supplementary key words eicosapentaenoic acid • liver X receptor {alpha} • sterol-regulatory element binding protein-1c • peroxisome proliferator-activated receptor {gamma} coactivator 1ß


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