FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets
FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets
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DOI：
10.1172/jci34090
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发表时间：
2008-08-01
影响因子：
15.9
通讯作者：
Kasuga, Masato
中科院分区：
文献类型：
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作者：
Nishino, Naonobu;Tamori, Yoshikazu;Kasuga, Masato
白色脂肪细胞是独一无二的，因为它们含有占据细胞质大部分的大的单眼脂滴。为了确定与成熟脂肪细胞维持相关的基因，我们在3T3-L1细胞中表达了显性-负性PPARγ，并进行了基因芯片筛选。在此背景下，27 kDa的脂肪特异性蛋白(FSP27)被强烈下调。FSP27在培养的前脂肪细胞中的表达与诱导分化有关，该蛋白在体内定位于小鼠白色脂肪细胞的脂滴中。在小鼠体内，FSP27的消融导致这些细胞内形成多房性脂滴。此外，FSP27缺陷小鼠可以免受饮食诱导的肥胖和胰岛素抵抗的影响，并由于白色脂肪组织(WAT)中线粒体生物合成的增加而表现出更高的代谢率。在培养的小鼠白色脂肪细胞中，FSP27被siRNA耗尽，导致大量小脂滴的形成，脂解增加，三酰甘油储存减少，而FSP27在COS细胞中的表达促进了大脂滴的形成。我们的结果表明，FSP27通过促进单眼脂滴的形成，从而限制脂解，从而有助于WAT中有效的能量储存。此外，我们发现WAT中脂质堆积的性质似乎与维持能量平衡和胰岛素敏感性有关。
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.