Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes.
Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes.
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DOI：
10.1016/j.jnutbio.2011.02.014
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发表时间：
2012-06
影响因子：
5.6
通讯作者：
McIntosh, Michael
中科院分区：
文献类型：
--
作者：
Obsen, Thomas;Faergeman, Nils J.;Chung, Soonkyu;Martinez, Kristina;Gobern, Semone;Loreau, Olivier;Wabitsch, Martin;Mandrup, Susanne;McIntosh, Michael
共轭亚油酸（CLA）在体内减少肥胖。然而，介导这些变化的机制尚不清楚。因此，我们用反式-10、顺式-12 CLA、顺式-9、反式-11 CLA或其他反式脂肪酸（FA）处理人脂肪细胞培养物，并测量脂质代谢指数。10，12共轭亚油酸的降脂作用是独特的，因为其他反式脂肪酸没有降低TG含量到相同的程度。使用低水平的[14 C]-CLA异构体，表明两种异构体都容易掺入酰基甘油和磷脂中，尽管其水平低于[14 C]-油酸或[14 C]-亚油酸。当使用[14 C]-乙酸和[14 C]-棕榈酸作为底物时，30 μM 10，12 CLA（而非9，11 CLA）可在3-24 h内降低甘油三酯（TG）、游离FA、甘油二酯、胆固醇酯、心磷脂、磷脂和神经酰胺的从头合成。用30 μM 10，12 CLA处理，而不是9，11 CLA，在3 d内降低细胞总脂质和单不饱和FA（MUFA）与饱和FA的比率，并在24 h内增加C18：0酰基辅酶A水平。与这些数据一致，硬脂酰辅酶A去饱和酶（SCD）-1 mRNA和蛋白水平下调10，12 CLA在7-12小时内，分别。10，12 CLA作用5 h后，肝X受体（LXR）α和固醇调节元件结合蛋白（SREBP）-1c的mRNA水平下降。这些数据表明，在从头脂质合成的异构体特异性减少10，12 CLA是由于，部分是由于快速抑制脂肪生成转录因子，调节MUFA的合成，这表明一个抗肥胖机制独特的反式FA。
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 CLA, cis-9, trans-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 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride (TG), free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids, and ceramides within 3–24 h. Treatment with 30 μM 10,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 d 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)α 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.
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影响因子：
1.9
作者：
Evans, M;Geigerman, C;McIntosh, M
通讯作者：
McIntosh, M
影响因子：
4.6
作者：
House, RL;Cassady, JP;Odle, J
通讯作者：
Odle, J
DOI：
10.1016/j.bbalip.2004.08.018
发表时间：
2005-02-21
影响因子：
4.8
作者：
Granlund, L;Pedersen, JI;Nebb, HI
通讯作者：
Nebb, HI
DOI：
10.1016/j.bbrc.2004.01.087
发表时间：
2004-03-12
影响因子：
3.1
作者：
Kang, KW;Miyazaki, M;Pariza, MW
通讯作者：
Pariza, MW
影响因子：
6.5
作者：
Kennedy, Arion;Overman, Angel;McIntosh, Michael
通讯作者：
McIntosh, Michael