J. Lipid Res.
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A more recent version of this article appeared on August 1, 2003

Papers In Press, published online ahead of print May 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300120-JLR200
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Submitted on March 17, 2003
Revised on May 12, 2003
Accepted on May 13, 2003

Trans10, cis12 conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator

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

Institute for Nutrition Research, University of Oslo, Oslo, Blindern 0316

Corresponding Author: 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 and trans10, cis12 CLA. A crude mixture of these isomers has in animal studies been shown to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the trans10, cis12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which trans10, cis12 CLA affects lipid accumulation in adipocytes. We have shown that trans10, cis12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 and 25 micromolar, respectively. Trans10, cis12 CLA fails to activate peroxisome proliferator-activated receptor gamma (PPARgamma), but selectively inhibits thiazolidinedione-induced PPARgamma activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with trans10, cis12 CLA alone, or in combination with Darglitazone, down regulate the mRNA expression of PPARgamma, as well as its target genes fatty acid binding protein (aP2) and liver X receptor alpha (LXRalpha). Taken together, our results suggest that the trans10, cis12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPARgamma modulator.


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