FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

被引：362

作者：

Nishino, Naonobu ^{[1
]}

Tamori, Yoshikazu ^{[1
]}

Tateya, Sanshiro ^{[1
]}

Kawaguchi, Takayuki ^{[1
]}

Shibakusa, Tetsuro ^{[2
]}

Mizunoya, Wataru ^{[2
]}

Inoue, Kazuo ^{[2
]}

Kitazawa, Riko ^{[3
]}

Kitazawa, Sohei ^{[3
]}

Matsuki, Yasushi ^{[4
]}

Hiramatsu, Ryuji ^{[4
]}

Masubuchi, Satoru ^{[5
]}

Omachi, Asako ^{[6
]}

Kimura, Kazuhiro ^{[6
]}

Saito, Masayuki ^{[7
]}

Amo, Taku ^{[8
]}

Ohta, Shigeo ^{[8
]}

Yamaguchi, Tomohiro ^{[9
]}

Osumi, Takashi ^{[9
]}

Cheng, Jinglei ^{[10
]}

Fujimoto, Toyoshi ^{[10
]}

Nakao, Harumi ^{[11
]}

Nakao, Kazuki ^{[12
]}

Aiba, Atsu ^{[11
]}

Okamura, Hitoshi

Fushiki, Tohru ^{[2
]}

Kasuga, Masato ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Endocrinol Diabet & Metab,Chuo Ku, Kobe, Hyogo 6500017, Japan

[2] Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Nutr Chem Lab, Kyoto, Japan

[3] Kobe Univ, Grad Sch Med, Dept Biomed Informat, Kobe, Hyogo 657, Japan

[4] Dainippon Sumitomo Pharma Co Ltd, Drug Res Div, Takarazuka, Hyogo, Japan

[5] Kobe Univ, Grad Sch Med, Dept Brain Sci, Kobe, Hyogo 657, Japan

[6] Hokkaido Univ, Grad Sch Vet Med, Dept Biomed Sci, Sapporo, Hokkaido, Japan

[7] Tenshi Coll, Sch Nursing & Nutr, Dept Nutr, Sapporo, Hokkaido, Japan

[8] Nippon Med Sch, Grad Sch Med, Dept Biochem & Cell Biol, Kawasaki, Kanagawa, Japan

[9] Univ Hyogo, Grad Sch Life Sci, Kamigori, Japan

[10] Nagoya Univ, Grad Sch Med, Dept Anat & Mol Cell Biol, Nagoya, Aichi 4648601, Japan

[11] Kobe Univ, Grad Sch Med, Dept Physiol & Cell Biol, Kobe, Hyogo 657, Japan

[12] RIKEN, Ctr Dev Biol, Lab Anim Resources & Genet Engn Team, Kobe, Hyogo, Japan

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 08期

关键词：

D O I：

10.1172/JCI34090

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPAR gamma in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

引用

页码：2808 / 2821

页数：14

共 53 条

[1] Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart [J].