Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet
Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet
复制标题
DOI：
10.1016/j.bbrc.2005.12.121
复制
发表时间：
2006-02-24
影响因子：
3.1
通讯作者：
Okumura, T
中科院分区：
文献类型：
--
作者：
Motomura, W;Inoue, M;Okumura, T
本研究旨在探讨脂肪分化相关蛋白（ADRP）在肝脏脂肪变性过程中的作用。免疫组化结果显示，与正常肝脏相比，脂肪肝患者肝细胞中ADRP的表达增加。ADRP的表达定位于肝细胞脂滴表面。在ob/ob小鼠的脂肪肝和高脂饮食引起的肝脏脂肪变性中，ADRP mRNA和蛋白的表达也同样升高。高脂饲料对肝脏中ADRP mRNA和蛋白的上调在脂滴表面呈时间依赖性。最近的研究表明，肝细胞中PPAR γ的上调与肝脏脂肪变性密切相关。为了阐明肝细胞中PPAR γ激活是否会增加ADRP的表达，我们检测了PPAR γ配体曲格列酮对HepG2细胞中ADRP mRNA表达的影响。曲格列酮使ADRP mRNA表达呈剂量依赖性和时间依赖性。上述结果提示，ADRP在人和小鼠肝脏脂肪变性中表达上调，高脂饮食通过激活PPAR γ增加ADRP的表达，进而诱导肝脏脂肪变性。(c) 2005爱思唯尔公司版权所有。
The present study was performed to examine a role of adipose differentiation-related protein (ADRP) in the process of liver steatosis. Immunohistochemical findings indicated that ADRP expression is increased in the hepatocytes in patients with fatty liver when compared with normal liver. ADRP expression is localized in the surface of lipid droplets in the hepatocytes. Increased expression of ADRP mRNA and protein was similarly observed in fatty liver in ob/ob mice and the liver steatosis induced by high fat diet in mice. The up-regulation of ADRP mRNA and protein in the liver by high fat diet was identified in the surface of lipid droplets in a time-dependent manner. Recent studies demonstrated that up-regulation of PPAR gamma in the hepatocytes is deeply involved in liver steatosis. To clarify whether ADRP expression is increased by PPAR gamma activation in hepatocytes, we examined the effect of a PPAR gamma ligand, troglitazone, on ADRP mRNA expression in HepG2 cells. ADRP mRNA expression was increased by troglitazone in dose- and time-dependent manners. All these results suggest that ADRP is up-regulated in liver steatosis in human and mice, and that high fat diet increases expression of ADRP through PPAR gamma activation, followed by induction of liver steatosis. (c) 2005 Elsevier Inc. All rights reserved.