Hepatic steatosis in leptin-deficient mice is promoted by the PPARγ target gene Fsp27
Hepatic steatosis in leptin-deficient mice is promoted by the PPARγ target gene Fsp27
复制标题
DOI：
10.1016/j.cmet.2008.03.003
复制
发表时间：
2008-04-01
期刊：
影响因子：
29
通讯作者：
Gonzalez, Frank J.
中科院分区：
文献类型：
--
作者：
Matsusue, Kimihiko;Kusakabe, Takashi;Gonzalez, Frank J.
过氧化物酶体增殖物激活受体γ（PPAR γ）在瘦素缺乏（ob/ob）小鼠肝脏中被诱导，并且对肝脂肪变性的发展至关重要。目前的研究表明，脂肪特异性蛋白27（Fsp 27）在ob/ob肝脏是一个直接的靶基因的过氧化物酶体增殖物激活受体γ，并能提高肝脏甘油三酯水平。FSP 27属于锡德家族，由锡德A、锡德B和FSP 27/锡德C组成，它们都含有保守的CIDE-N结构域。最近报道FSP 27是一种脂滴结合蛋白，并促进脂肪细胞中的脂质积累。Fsp 27基因在oblob肝脏中以高水平表达，而在缺乏PPAR γ的oblob肝脏中以明显较低的水平表达。在体外或体内，腺病毒在肝细胞中强制表达FSP 27导致甘油三酯水平增加。与对照腺病毒感染的肝脏相比，通过表达FSP 27 shRNA的腺病毒敲低导致肝脏甘油三酯的积累较低。总之，这些结果表明FSP 27是PPAR γ依赖性肝脂肪变性的直接介质。
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is induced in leptin-deficient(ob/ob) mouse liver and is critical for the development of hepatic steatosis. The present study shows that fat-specific protein 27 (Fsp27) in ob/ob liver is a direct target gene of PPAR gamma and can elevate hepatic triglyceride levels. FSP27 belongs to the CIDE family, composed of CIDE A, CIDE B, and FSP27/CIDE C, all of which contain a conserved CIDE-N domain. FSP27 was recently reported to be a lipid droplet-binding protein and to promote lipid accumulation in adipocytes. The Fsp27 gene was expressed at high levels in oblob liver and at markedly lower levels in oblob livers lacking PPAR gamma. Forced expression of FSP27 by adenovirus in hepatocytes in vitro or in vivo led to increased triglyceride levels. Knockdown by adenovirus expressing FSP27 shRNA resulted in lower accumulation of hepatic triglycerides compared to control adenovirus-infected liver. Taken together, these results indicate that FSP27 is a direct mediator of PPAR gamma-dependent hepatic steatosis.