Increased expression of PPARγ in high fat diet-induced liver steatosis in mice
Increased expression of PPARγ in high fat diet-induced liver steatosis in mice
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DOI：
10.1016/j.bbrc.2005.08.070
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发表时间：
2005-10-14
影响因子：
3.1
通讯作者：
Okumura, T
中科院分区：
文献类型：
--
作者：
Inoue, M;Ohtake, T;Okumura, T
本研究的目的是检验过氧化物酶体增殖物激活受体γ（PPARγ）与高脂肪饮食诱导的肝脏脂肪变性有关的假设。小鼠分别喂食含有大约10%或80%胆固醇的对照饮食或高脂肪饮食。宏观和微观结果表明，早在高脂饮食2周后就观察到肝脏中的脂质积累，并且高脂饮食12周形成脂肪肝表型，建立了饮食诱导的肝脏脂肪变性的新模型。微阵列基因分析和实时PCR研究表明，在参与脂质代谢的基因、脂肪生成相关基因、PPARγ及其靶基因中，高脂肪饮食两周后肝脏中CD36 mRNA的表达特异性上调。免疫组织化学研究表明，高脂肪饮食会增加肝细胞核中 PPAR γ 蛋白的表达。研究还表明，肝脏中 PPAR γ 的上游分子 cAMP 反应元件结合蛋白 (CREB) 的蛋白表达受到高脂肪饮食的显着抑制。这些结果首次提示CREB-PPARγ信号通路可能参与高脂饮食诱导的肝脏脂肪变性。 (c) 2005 Elsevier Inc. 保留所有权利。
The present study was performed to examine a hypothesis that peroxisome proliferator-activated receptor gamma (PPAR gamma) is implicated in high fat diet-induced liver steatosis. Mice were fed with control or high fat diet containing approximately 10% or 80% cholesterol, respectively. Macroscopic and microscopic findings demonstrated that lipid accumulation in the liver was observed as early as 2 weeks after high fat diet and that high fat diet for 12 weeks developed a fatty liver phenotype, establishing a novel model of diet-induced liver steatosis. Gene profiling with microarray and real-time PCR studies demonstrated that among genes involved in lipid metabolism, adipogenesis-related genes, PPAR gamma and its targeted gene, CD36 mRNA expression was specifically up-regulated in the liver by high fat diet for 2 weeks. Irnmunohistochemical study revealed that PPAR gamma protein expression is increased in the nuclei of hepatocytes by high fat diet. It was also shown that protein expression of cAMP response element-binding protein (CREB), an upstream molecule of PPAR gamma, in the liver was drastically suppressed by high fat diet. All these results suggest for the first time that the CREB-PPAR gamma signaling pathway may be involved in the high fat diet-induced liver steatosis. (c) 2005 Elsevier Inc. All rights reserved.