Promotion of lipogenesis by PPARγ-activated FXR expression in adipocytes
Promotion of lipogenesis by PPARγ-activated FXR expression in adipocytes
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DOI：
10.1016/j.bbrc.2020.04.075
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发表时间：
2020-06-18
影响因子：
3.1
通讯作者：
Fujimori, Ko
中科院分区：
文献类型：
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作者：
Shinohara, Saki;Fujimori, Ko
法尼醇X受体(FXR)是一种胆汁酸受体，已知参与促进脂肪生成。然而，FXR促进脂肪生成的调控机制尚不清楚。在本研究中，我们研究了FXR介导的小鼠脂肪细胞3T3-L1细胞成脂激活的调控机制。FXR激动剂鹅去氧胆酸(CDCA)可促进细胞内甘油三酯的积累，促进成脂基因和成脂基因的表达，而FXR拮抗剂谷固酮则抑制CDCA激活的脂肪生成。此外，过氧化物酶体增殖物激活受体(PPAR)γ激动剂曲格列酮在脂肪形成过程中上调了FXR基因的表达，与PPAR伽马基因的表达相似。染色质免疫沉淀分析表明，PPARγ以依赖于PPARγ激动剂的方式与FXR基因的PPAR反应元件结合。此外，FXR激活诱导了脂肪细胞中硬脂酰辅酶A脱饱和酶(SCD)基因的表达。在SCD基因启动子中发现了FXR反应元件(FXRE)，FXR与SCD基因启动子的FXRE结合，CDCA可增强其在脂肪细胞中的结合效率。这些结果表明，FXR通过以PPARγ依赖的方式增强SCD在脂肪细胞中的表达来促进脂肪生成，这使得本研究首次确定了FXR在PPAR伽马激活促进脂肪生成中的作用。(C)2020 Elsevier Inc.保留所有权利。
Farnesoid X receptor (FXR), a bile acid receptor, is known to be involved in the promotion of adipogenesis. However, the regulation mechanism of FXR-promoted adipogenesis remains unclear. In this study, we investigated the regulation mechanism of FXR-mediated activation of adipogenesis in murine adipocyte 3T3-L1 cells. Chenodeoxycholic acid (CDCA), a potent FXR agonist, enhanced the accumulation of intracellular triglycerides and the expression of the adipogenic and lipogenic genes, while guggulsterone, an FXR antagonist, suppressed CDCA-activated adipogenesis. Moreover, troglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, elevated the expression of the FXR gene during adipogenesis, similar to that of the PPAR gamma gene. Chromatin immunoprecipitation assay demonstrated that PPAR gamma bound to the PPAR-responsive element of the FXR gene in a PPAR gamma agonist-dependent manner. Furthermore, FXR activation induced the expression of the stearoyl-CoA desaturase (SCD) gene in adipocytes. The FXR-response element (FXRE) was found in the SCD gene promoter, and FXR bound to the FXRE of the SCD gene promoter, and its binding efficiency was enhanced by CDCA in adipocytes. These results indicate that FXR assisted lipogenesis through the enhanced expression of SCD in a PPAR gamma-dependent manner in adipocytes, making this study the first to identify the role of FXR in the promotion of lipogenesis by PPAR gamma activation. (c) 2020 Elsevier Inc. All rights reserved.