High expression of liver histone deacetylase 3 contributes to high-fat-diet-induced metabolic syndrome by suppressing the PPAR-γ and LXR-α-pathways in E3 rats
High expression of liver histone deacetylase 3 contributes to high-fat-diet-induced metabolic syndrome by suppressing the PPAR-γ and LXR-α-pathways in E3 rats
复制标题
DOI：
10.1016/j.mce.2011.06.028
复制
发表时间：
2011-09-15
影响因子：
4.1
通讯作者：
Lu, Shemin
中科院分区：
文献类型：
--
作者：
Li, Dongmin;Wang, Xuan;Lu, Shemin
在之前的实验中，我们发现E3大鼠和DA.1U大鼠对高脂肪饮食诱导代谢综合征（high-fat-diet-induced metabolic syndrome, HFD-MetS）的反应不同。本研究旨在探讨E3大鼠与DA.1U大鼠代谢综合征易感性遗传差异的原因及分子机制。首先，建立E3和DA.1U大鼠12周HFD-MetS模型并进行评估。然后，通过不同的方法测定胰岛素关键信号分子、代谢核受体、代谢关键酶和组蛋白去乙酰化酶（Hdacs）的表达。最后，我们在DA.1U和E3大鼠的CBRH-7919细胞和原代肝细胞中分析了Hdac3过表达和破坏对代谢性核受体的影响。我们发现E3大鼠对HFD-MetS有易感，而DA.1U大鼠对HFD-MetS有抗性。肝X受体α、β （lxr - α、β）、法脂类X受体（FXR）、过氧化物酶体增殖物激活受体γ (ppar - γ)和胆固醇7 α -羟化酶（CYP7A1）的表达在DA.1U大鼠肝脏中显著升高，而在E3大鼠肝脏中显著降低。HFD处理在E3和DA. 1u大鼠肝脏中Hdac3的表达均升高，但DA大鼠肝脏中Hdac3的组成性表达较低。IU大鼠肝脏比E3大鼠肝脏。重要的是，过表达Hdac3可以下调CBRH-7919细胞和原代培养的DA肝细胞中lxr - α、ppar - γ和CYP7A1的表达。IU老鼠。相反，shRNA对Hdac3的破坏上调了CBRH-7919细胞和E3大鼠原代培养肝细胞中lxr - α、ppar - γ和CYP7A1的表达。结果表明，hdac - 3的高组成表达抑制肝脏中ppar - γ、lxr - α和CYP7A1的表达有助于E3大鼠的HFD-MetS。2011爱思唯尔爱尔兰有限公司版权所有。
In the previous experiment, we found that there was a different response between E3 rats and DA.1U rats to high-fat-diet-induced metabolic syndrome (HFD-MetS). The aim of this study was to explore the cause and molecular mechanism of the genetic difference in susceptibility to metabolic syndrome in E3 rats as compared with DA.1U rats. Firstly, a 12-week HFD-MetS model in E3 and DA.1U rats was carried out and assessed. Then, the expression of key insulin signaling molecules, metabolic nuclear receptors, metabolic key enzymes and histone deacetylases (Hdacs) was determined by different methods. Finally, the effects of overexpression and disruption of Hdac3 on metabolic nuclear receptors were analyzed in CBRH-7919 cells and primarily-hepatic cells from DA.1U and E3 rats. We found that E3 rats were susceptible, while DA.1U rats were resisted to HFD-MetS. The expression of liver X receptor alpha,beta (LXR-alpha,beta), farnesoid X receptor (FXR), peroxisome proliferator activated receptor gamma (PPAR-gamma) and cholesterol 7 alpha-hydroxylase (CYP7A1) increased markedly in DA.1U rat liver, whereas they decreased significantly in E3 rats. The expression of Hdac3 increased by HFD treatment in both E3 and DA.1U rat livers, but the constitutive Hdac3 expression was lower in DA.IU rat liver than in E3 rat liver. Importantly, overexpression of Hdac3 could downregulate the expression of LXR-alpha, PPAR-gamma and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from DA.IU rats. On the contrary, disruption of Hdac3 by shRNA upregulated the expression of LXR-alpha, PPAR-gamma and CYP7A1 in both CBRH-7919 cells and primarily cultured hepatic cells from E3 rats. The results suggested that a high constitutive expression of Hdac3 inhibiting the expression of PPAR-gamma, LXR-alpha and CYP7A1 in liver contributes to HFD-MetS in E3 rats. (C) 2011 Elsevier Ireland Ltd. All rights reserved.