Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator
Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARγ modulator
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DOI：
10.1194/jlr.m300120-jlr200
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发表时间：
2003-08-01
影响因子：
6.5
通讯作者：
Nebb, HI
中科院分区：
文献类型：
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作者：
Granlund, L;Juvet, LK;Nebb, HI
在反刍动物产品中发现了一组称为共轭亚油酸（CLA）的多不饱和脂肪酸，其中最常见的异构体是cis 9，trans 11（c9，t11）和trans 10，cis 12（t10，c12）CLA。这些异构体的粗混合物在动物研究中显示出通过减少体脂肪量以及增加瘦体重来改变身体组成，其中t10，c12异构体具有最显著的效果。本研究的目的是建立t10，c12共轭亚油酸影响脂质积累的分子机制。脂肪细胞我们已经证明，t10，c12 CLA在分别低至5 μ M和25 μ M的浓度下防止人和小鼠脂肪细胞中的脂质积聚，t10，c12 CLA不能激活过氧化物酶体增殖物激活受体γ（PPARgamma），但选择性地抑制噻唑烷二酮诱导的3 T3-L1脂肪细胞中PPARgamma的激活。单独使用t10、c12 CLA或与达格列酮联合使用处理成熟脂肪细胞可下调PPAR γ及其靶基因、脂肪酸结合蛋白（aP 2）和肝脏X受体α（LXR α）的mRNA表达。总之，我们的结果表明，反式10，顺式12 CIA异构体通过作为PPARgamma调节剂防止脂肪细胞中的脂质积累。
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. 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 muM and 25 muM, 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). jlr Taken together, our results suggest that the trans10, cis12 CIA isomer prevents lipid accumulation in adipocytes by acting as a PPARgamma modulator.