Regulation of gene expression by FSP27 in white and brown adipose tissue.
Regulation of gene expression by FSP27 in white and brown adipose tissue.
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FSP27 在白色和棕色脂肪组织中基因表达的调节
DOI：
10.1186/1471-2164-11-446
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发表时间：
2010-07-22
期刊：
影响因子：
4.4
通讯作者：
Sang J
中科院分区：
文献类型：
--
作者：
Li D;Zhang Y;Xu L;Zhou L;Wang Y;Xue B;Wen Z;Li P;Sang J
褐色和白色脂肪组织（BAT和WAT）在控制能量稳态和肥胖和糖尿病的发生中起着关键作用。小鼠脂肪特异性蛋白27 （FSP27）是诱导细胞死亡的dff45样效应物（CIDE）家族的一员，在BAT和WAT中均有表达，并与脂滴相关。FSP27的过度表达促进了脂质储存，而FSP27缺陷小鼠具有改善的胰岛素敏感性，并且对饮食引起的肥胖具有抵抗力。此外，fsp27缺陷的白色脂肪细胞脂质储存减少，脂滴更小，线粒体活性增加，几种bat选择性基因表达增加。为了阐明FSP27控制WAT和BAT中脂质储存和基因表达的分子机制，我们通过芯片分析系统地分析了缺乏sp27的WAT的基因表达谱，并通过半定量实时PCR分析比较了WAT和BAT中特定基因的表达水平。结果在WAT offsp27缺失小鼠中，bat选择基因显著上调，而WAT选择基因显著下调。在瘦素/ fsp27双缺陷小鼠的WAT中，bat选择基因的表达也显著上调。此外，在fsp27缺失的WAT中，参与氧化磷酸化、TCA循环、脂肪酸合成和脂肪酸氧化等多种代谢途径的基因表达水平升高。相反，在fsp27缺失的WAT中，参与细胞外基质重塑、经典补体通路和TGF-β信号通路的基因表达水平下调。最重要的是，决定BAT身份的调节因子，如CEBPα/β、PRDM16和cAMP途径的主要成分，在WAT offsp27缺陷小鼠中表达水平显著上调。在瘦素/ fsp27双缺陷小鼠中，这些调节因子的表达水平也上调。有趣的是，在BAT offsp27缺陷小鼠中观察到不同的基因表达谱。综上所述，这些数据表明WAT offsp27缺陷小鼠具有与BAT相似的基因表达谱。结论sfsp27作为一个分子决定因子，控制多种代谢和信号通路的基因表达，特别是CEBPα/β、PRDM16和cAMP信号通路成分等调控因子的表达，控制WAT和BAT的身份。
BackgroundBrown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereasFSP27deficient mice have improved insulin sensitivity and are resistant to diet-induced obesity. In addition,FSP27-deficient white adipocytes have reduced lipid storage, smaller lipid droplets, increased mitochondrial activity and a higher expression of several BAT-selective genes. To elucidate the molecular mechanism by which FSP27 controls lipid storage and gene expression in WAT and BAT, we systematically analyzed the gene expression profile ofFSP27-deficient WAT by microarray analysis and compared the expression levels of a specific set of genes in WAT and BAT by semi-quantitative real-time PCR analysis.ResultsBAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT ofFSP27-deficient mice. The expression of the BAT-selective genes was also dramatically up-regulated in the WAT ofleptin/FSP27double deficient mice. In addition, the expression levels of genes involved in multiple metabolic pathways, including oxidative phosphorylation, the TCA cycle, fatty acid synthesis and fatty acid oxidation, were increased in theFSP27-deficient WAT. In contrast, the expression levels for genes involved in extracellular matrix remodeling, the classic complement pathway and TGF-β signaling were down-regulated in theFSP27-deficient WAT. Most importantly, the expression levels of regulatory factors that determine BAT identity, such as CEBPα/β, PRDM16 and major components of the cAMP pathway, were markedly up-regulated in the WAT ofFSP27-deficient mice. The expression levels of these regulatory factors were also up-regulated inleptin/FSP27double deficient mice. Interestingly, distinct gene expression profiles were observed in the BAT ofFSP27-deficient mice. Taken together, these data suggest that the WAT ofFSP27-deficient mice have a gene expression profile similar to that of BAT.ConclusionsFSP27 acts as a molecular determinant that controls gene expression for a diversity of metabolic and signaling pathways and, in particular, the expression of regulatory factors, including CEBPα/β, PRDM16 and components of the cAMP signaling pathway, that control the identity of WAT and BAT.