Abstract
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 microM and 25 microM, respectively. t10,c12 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 t10,c12 CLA alone or in combination with Darglitazone down-regulates 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.
Highlights
A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis9, trans11 (c9,t11) and trans10, cis12 (t10,c12) CLA
We have demonstrated that even though t10,c12 CLA is not a peroxisome proliferator-activated receptor (PPAR)␥ ligand, it is able to reduce Darglitazone-induced PPAR␥ activation and down-regulate Darglitazone-induced gene expression of PPAR␥ and the target genes fatty acid binding protein and liver X receptor ␣ (LXR␣) in mature adipocytes
Combining the relevance of human and animal studies in vivo with the power of in vitro adipocyte models is important to better understand the role of CLA isomers in body fat accumulation. This stimulated us to study the molecular mechanisms by which CLA isomers mediate their effects in adipose cell models
Summary
A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis, trans (c9,t11) and trans, cis (t10,c12) CLA. Our results suggest that the trans, cis CLA isomer prevents lipid accumulation in adipocytes by acting as a PPAR␥ modulator.— Granlund, L., L. Cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPAR␥ modulator. Interest in the PPAR␥ receptor field increased when a new class of synthetic antidiabetic drugs, the thiazolidinediones (TZDs), were shown to act as high-affinity ligands for PPAR␥ [4]. The effects of these ligands are mediated by changes in the transcriptional rate of PPAR␥ target genes [11].
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