Cell Metabolism：瘦素调节肝脏处脂肪积累
在2008年4月9日出版的《细胞—代谢》（Cell Metabolism）上，来自美国和日本的一组科学家发表文章称，脂肪特异性蛋白27（fat-specific protein 27，Fsp27）在缺乏瘦素的肝脏中是PPARγ的直接目标基因，并且能提高肝脏甘油三酯（hepatic triglyceride）的水平。FSP27属于CIDE家族的一种，目前在CIDE家族中，已经发现3个人类CIDE蛋白：CIDE A、CIDE B、CIDE 3，以及3个鼠CIDE蛋白：CIDE A、CIDE B、FSP27，它们都含有一种CIDE-N域。
最近有报导表示，FSP27是一种脂肪液滴结合蛋白，并且会促进脂肪细胞（adipocyte）中脂类物质的堆积。在缺乏瘦素的ob/ob细胞中，FSP27基因会得到很高水平的表达，而相反，在缺少PPARγ的ob/ob肝脏组织中，该基因的表达程度变得相当低。在试管以及活体实验条件下，腺病毒（adenovirus）会使肝细胞（hepatocyte）中FSP27强迫表达，并最终增加甘油三酯的含量。在实验中科学家发现，相比较感染了腺病毒的肝脏而言，去除腺病毒FSP27表达影响的肝脏中甘油三酯的聚集程度较低。因此科学家们认为，对于PPARγ导致的脂肪肝形成，FSP27是一种直接调节因子。（科学网 何宏辉/编译）
瘦素：
瘦素（leptin）是一种含有167个氨基酸的蛋白质，它具有抑制食欲、减少饮食摄入量、促进能量消耗以及抑制脂肪合成的作用。而肥胖基因（ob）对瘦素具有一定影响，人类ob基因位于第7号染色体，小鼠ob基因则位于第6号染色体。在缺乏瘦素的老鼠（ob/ob mouse）肝脏中，会诱导产生一种过氧化体增殖物激活受体γ（peroxisome proliferator-activated receptor，简称PPARγ），这种物质对于肝脂肪变性（hepatic steatosis）的发生非常关键。
生物谷推荐原始出处：
（Cell Metabolism），Vol 7, 302-311, 09 April 2008，Kimihiko Matsusue, Frank J. Gonzalez
Hepatic Steatosis in Leptin-Deficient Mice Is Promoted by the PPARγ Target Gene Fsp27
Kimihiko Matsusue,1,2,
Takashi Kusakabe,3 Takahiro Noguchi,2 Shouichi Takiguchi,4 Toshimitsu Suzuki,3 Shigeru Yamano,2,5 and Frank J. Gonzalez1,5
1 Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2 Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
3 Department of Pathology, Fukushima Medical University School of Medicine, 1 Hikariga-oka, Fukushima City, Fukushima 960-1295, Japan
4 Institute for Clinical Research, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan
Summary
Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 ob/ob liver and at markedly lower levels in ob/ob livers lacking PPARγ. 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 PPARγ-dependent hepatic steatosis.
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