Liver X receptor preferentially activates de novo lipogenesis in human preadipocytes
Liver X receptor preferentially activates de novo lipogenesis in human preadipocytes
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DOI：
10.1016/j.biochi.2005.08.010
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发表时间：
2006-03-01
期刊：
影响因子：
3.9
通讯作者：
Macé, K
中科院分区：
文献类型：
--
作者：
Darimont, C;Avanti, O;Macé, K
肝脏X受体（LXR）被证明在肝脏胆固醇代谢中发挥关键作用。肠和巨噬细胞。然而，由于报道的结果相互矛盾，其对前脂肪细胞分化调节的功能仍不清楚。本研究的目的是揭示 LXR 在人类前脂肪细胞中的功能。我们发现，LXR 激动剂 T0901317 强烈刺激人前脂肪细胞系 Chub-S7 以及人原代基质血管成分 (SVF) 细胞中 SREBP-1c 以及脂肪生成酶 ACC-1、IFAS 和 SCD-1 的表达。对基因表达的影响与刺激两种细胞模型中的从头脂肪生成有关，从而诱导脂质积累。与 PPAR-γ 激动剂 (BRL49653) 相反。 T0901317仅轻微增强Chub-S7细胞中PPARγ依赖性基因（PPARγ、aP2和脂联素）的表达，并且未能改变它们在人SVF细胞中的表达。这些结果表明，LXR 通过诱导从头脂肪生成优先刺激人前脂肪细胞中甘油三酯的积累，而不是通过 PPAR γ 激活来激活分化过程。 (c) 2005 年爱思唯尔 SAS。版权所有。
The liver X receptor (LXR) was demonstrated to play a key role in cholesterol metabolism in liver. intestine and macrophage. However, its function on the regulation of preadipocyte differentiation remains unclear since contradictory results were reported. The objective of the present study was to unravel the functionality of LXR in human preadipocytes. We show that the LXR agonist T0901317 strongly stimulated the expression of SREBP-1c and the lipogenic enzymes ACC-1, IFAS and SCD-1 in both the human preadipose cell line Chub-S7 as well as human primary stromal vascular fraction (SVF) cells. The effects on gene expression were associated with the stimulation of de novo lipogenesis in both cell models, resulting in the induction of lipid accumulation. In contrast with a PPAR-gamma agonist (BRL49653). T0901317 enhanced only slightly the expression of PPAR gamma dependent genes (PPAR gamma, aP2 and adiponectin) in Chub-S7 cells and failed to change their expression in human SVF cells. These results show that LXR stimulated preferentially triglyceride accumulation in human preadipocytes via the induction of de novo lipogenesis, rather than activating the differentiation process through PPAR gamma activation. (c) 2005 Elsevier SAS. All rights reserved.