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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300120-JLR200 on May 16, 2003

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Journal of Lipid Research, Vol. 44, 1441-1452, August 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPAR{gamma} modulator

Linda Granlund, Lene K. Juvet, Jan I. Pedersen and Hilde I. Nebb1

Institute for Nutrition Research, University of Oslo, N-0316 Oslo, Norway

1 To whom correspondence should be addressed. e-mail: h.i.nebb{at}basalmed.uio.no

A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 (c 9,t11) and trans10, cis12 (t10,c12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t10,c12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t10,c12 CLA affects lipid accumulation in adipocytes. We have shown that t10,c12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 µM and 25 µM, respectively. t10,c12 CLA fails to activate peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) but selectively inhibits thiazolidinedione-induced PPAR{gamma} activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t10,c12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPAR{gamma} as well as its target genes, fatty acid binding protein (aP2) and liver X receptor {alpha} (LXR{alpha}).

Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPAR{gamma} modulator.

Abbreviations: aP2, fatty acid binding protein (also known as aFABP); CLA, conjugated linoleic acid; LXR, liver X receptor; PPAR, peroxisome proliferator-activated receptor; RXR, retinoid X receptor; SGBS, Simpson-Golabi-Behmel syndrome; TAG, triacylglycerol, TZD, thiazolidinediones

Supplementary key words fatty acid binding protein • liver X receptor • Darglitazone


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