Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

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• 作者：Thomas Obsen^a ; Nils J. Faergeman^a ; Soonkyu Chung^b ; Kristina Martinez^c ; Semone Gobern^c ; Olivier Loreau^d ; Martin Wabitsch^e ; Susanne Mandrup^a ; Michael McIntosh^c ; ^{mkmcinto@uncg.edu}
• 关键词：aP2/FABP4 ; adipocyte fatty acid binding protein 4 ; BSA ; bovine serum albumin ; CLA ; conjugated linoleic acid ; DGAT2 ; diacylglycerol transferase-2 ; ER ; endoplasmic reticulum ; EA ; elaidic acid ; EOS ; ceramide-containing sphingosine ; FA ; fatty acids ; FAME ; fat
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2012
• 期刊代码：70_09552863
• 类别：abs
• 出版时间：June, 2012
• 卷：23
• 期：6
• 页码：580-590
• 文件大小：1753 K

摘要

Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid metabolism. The lipid-lowering effects of 10,12 CLA were unique, as other trans FA did not reduce TG content to the same extent. Using low levels of [¹⁴C]-CLA isomers, it was shown that both isomers were readily incorporated into acylglycerols and phospholipids, albeit at lower levels than [¹⁴C]-oleic or [¹⁴C]-linoleic acids. When using [¹⁴C]-acetic acid and [¹⁴C]-pyruvic acid as substrates, 30 渭M 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 渭M 10,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within 7-12 h, respectively. The mRNA levels of liver X receptor (LXR)伪 and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA.