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[肝脏脂质蓄积的新机制:肝脏PPARγ-fsp27信号的生理作用]

[Novel mechanism for hepatic lipid accumulation: a physiological role for hepatic PPARγ-fsp27 signal].

作者信息

Matsusue Kimihiko

机构信息

Faculty of Pharmaceutical Science, Fukuoka University, Japan.

出版信息

Yakugaku Zasshi. 2012;132(7):823-9. doi: 10.1248/yakushi.132.823.

DOI:10.1248/yakushi.132.823
PMID:22790028
Abstract

Fat-specific protein 27 (fsp27) was originally isolated by screening for genes specifically expressed in fully differentiated mouse adipocytes. Fsp27 and cell death-inducing DFF45-like effector (CIDE) C, the human homologue of fsp27, belong to the CIDE family. Fsp27, which is highly expressed in mouse white and brown adipose tissues, was recently reported to be a lipid droplet (LD)-binding protein that promotes lipid accumulation in adipocytes. In contrast, we showed that fsp27 was also expressed in the fatty liver of the ob/ob type II diabetes model mouse. The expression of fsp27 was markedly decreased in livers lacking the nuclear receptor peroxisome proliferator-activated receptor γ(PPARγ). A functional PPAR response element site was identified in the fsp27 promoter region. Forced expression of fsp27 in hepatocytes in vitro or in vivo led to increased LD through increased triglyceride levels. The current status of the physiological roles of the PPARγ-fsp27 signal in fatty liver are discussed along with its significance as a factor involved in the development of metabolic disorders.

摘要

脂肪特异性蛋白27(fsp27)最初是通过筛选在完全分化的小鼠脂肪细胞中特异性表达的基因而分离得到的。Fsp27和细胞死亡诱导DFF45样效应蛋白(CIDE)C(fsp27的人类同源物)属于CIDE家族。Fsp27在小鼠白色和棕色脂肪组织中高度表达,最近有报道称它是一种脂滴(LD)结合蛋白,可促进脂肪细胞中的脂质积累。相比之下,我们发现fsp27在ob/ob II型糖尿病模型小鼠的脂肪肝中也有表达。在缺乏核受体过氧化物酶体增殖物激活受体γ(PPARγ)的肝脏中,fsp27的表达明显降低。在fsp27启动子区域鉴定出一个功能性PPAR反应元件位点。在体外或体内肝细胞中强制表达fsp27会通过增加甘油三酯水平导致脂滴增加。本文讨论了PPARγ - fsp27信号在脂肪肝中的生理作用现状及其作为参与代谢紊乱发展的一个因素的意义。

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