Impaired lipid accumulation by trans 10, cis 12 CLA during adipocyte differentiation is dependent on timing and length of treatment
Impaired lipid accumulation by trans 10, cis 12 CLA during adipocyte differentiation is dependent on timing and length of treatment
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DOI：
10.1016/j.bbalip.2004.08.018
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发表时间：
2005-02-21
影响因子：
4.8
通讯作者：
Nebb, HI
中科院分区：
文献类型：
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作者：
Granlund, L;Pedersen, JI;Nebb, HI
共轭亚油酸(CLAS)是一类存在于反刍动物产品中的多不饱和脂肪酸，其主要异构体为cis9，tr11(c9，t11)和tr10，cis12(t10，c12)CLA。我们之前已经证明，t10，c12CLA防止成熟脂肪细胞中的脂质堆积部分是通过作为过氧化酶体增殖物激活受体伽马(PPARGamma)调节剂来发挥作用的。这项研究的目的是进一步建立t10，c12共轭亚油酸抑制脂肪堆积的分子机制，重点是在脂肪形成过程中的治疗时间点和持续时间。结果表明，t10，c12共轭亚油酸处理对分化早期(d(D)0-6)的抑制作用最强。在此期间的治疗足以防止成熟脂肪细胞中的脂肪堆积。成脂标志物基因PPARGamma和CCAAT/增强子结合蛋白α(C/EBPalpha)在治疗后D0-6期间均下调，而另外的治疗也下调了固醇调节元件结合蛋白-1c(SREBP-1c)、肝脏X受体α(LXRpha)、脂肪酸结合蛋白(AP2)、脂肪酸转位酶(CD36)和胰岛素敏感葡萄糖转运蛋白4(GLUT4)的表达。T10、c12共轭亚油酸的这些作用反映了随后观察到的成熟脂肪细胞中脂肪堆积的减弱。有趣的是，早期B细胞因子(O/E-1)被认为促进脂肪生成，并参与控制对终末脂肪细胞分化至关重要的基因，但不受t10，c12CLA治疗的影响。综上所述，我们的数据表明，在脂肪细胞分化过程中，抑制t10，c12CLA诱导的脂肪积累与早期(PPARGamma和C/EBPalpha)和晚期(LXRpha，aP2和CD36)成脂标记基因之间的紧密调控串扰有关。(C)2004爱思唯尔B.V.保留所有权利。
Conjugated linoleic acids (CLAs) are a group of polyunsaturated fatty acids found in ruminant products, where the predominant isomers are cis9, trans11 (c9,t11) and trans10, cis12 (t10,c12) CLA. We have previously shown that t10,c12 CLA prevents lipid accumulation ill mature adipocytes in part by acting as a peroxisome proliferator-activated receptor gamma (PPARgamma) modulator. The objective of this study was to further establish the molecular mechanisms underlying the attenuating effect on lipid accumulation by t10,c12 CLA, with focus on time point and duration of treatment during adipogenesis. We have shown that t10,c 12 CLA treatment has its most attenuating effect early (day (D) 0-6) during differentiation. Treatment during this period is sufficient to prevent lipid accumulation in mature adipocytes. The adipogenic marker genes PPARgamma and CCAAT/enhancer binding protein alpha (C/EBPalpha) are both down-regulated after treatment within the period from D0-6, while additional treatment also down-regulates the expression of sterol regulatory element binding protein-1c (SREBP-1c), liver X receptor alpha (LXRalpha), fatty acid binding protein (aP2), fatty acid translocase (CD36) and insulin-sensitive glucose transporter 4 (GLUT4). These effects of t10,c12 CLA reflect the subsequent attenuation of lipid accumulation observed in mature adipocytes. Interestingly, the early B-cell factor (O/ E-1), which is known to promote adipogenesis and to be involved in control of genes important for terminal adipocyte differentiation, is unaffected by treatment of t10,c12 CLA. Taken together, our data indicate that inhibition of lipid accumulation induced by t10,c12 CLA treatment during adipocyte differentiation is associated with a tight regulatory cross-talk between early (PPARgamma and C/EBPalpha) and late (LXRalpha, aP2 and CD36) adipogenic marker genes. (C) 2004 Elsevier B.V. All rights reserved.