TRB3 suppresses adipocyte differentiation by negatively regulating PPARγ transcriptional activity
TRB3 suppresses adipocyte differentiation by negatively regulating PPARγ transcriptional activity
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DOI：
10.1194/jlr.m700545-jlr200
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发表时间：
2008-04-01
影响因子：
6.5
通讯作者：
Sato, Ryuichiro
中科院分区：
文献类型：
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作者：
Takahashi, Yu;Ohoka, Nobumichi;Sato, Ryuichiro
在努力确定过氧化物酶体增殖物激活受体γ（PPARgamma）依赖的围脂蛋白基因表达的调节剂的过程中，我们发现，tribbles同系物3（TRB 3），含有一个单一的激酶结构域没有酶活性，下调PPARgamma转录活性的蛋白质-蛋白质相互作用。我们研究了TRB 3在3 T3-LI细胞中脂肪细胞分化中的作用。TRB 3基因和蛋白表达增加，伴随着在脂肪细胞分化的CCAAT/增强子结合蛋白同源蛋白的mRNA水平的增加。TRB 3和PPAR γ之间的物理相互作用也在3 T3-L1脂肪细胞中得到验证。在3 T3-LI细胞中强制TRB 3表达降低了PPAR γ靶基因的mRNA水平和细胞内甘油三酯水平，而通过RNA干扰敲低TRB 3表达增加了它们。TRB 3还抑制慢病毒介导的表达PPAR γ的3 T3-LI细胞中的PPAR γ依赖性脂肪细胞分化。这些结果提供了TRB 3作为脂肪细胞分化的主要调节剂的PPARgamma的有效负调节剂，并严格控制脂肪形成的证据。
In the course of an effort to identify the regulators for peroxisome proliferator-activated receptor gamma (PPAR gamma)-dependent perilipin gene expression, we found that tribbles homolog 3 (TRB3), containing a single kinase domain without enzymatic activity, downregulates PPAR gamma transcriptional activities by protein-protein interaction. We examined the role that TRB3 plays in adipocyte differentiation in 3T3-LI cells. TRB3 gene and protein expression was increased during adipocyte differentiation concomitantly with an increase in the mRNA levels of CCAAT/enhancer binding protein homologous protein. The physical interaction between TRB3 and PPAR gamma was also verified in 3T3-LI adipocytes. Forced TRB3 expression in 3T3-LI cells decreased the mRNA levels of PPAR gamma-target genes and intracellular triglyceride levels, whereas knockdown of TRB3 expression by RNA interference increased them. TRB3 also inhibits PPAR gamma-dependent adipocyte differentiation in lentivirus-mediated PPAR gamma-expressing 3T3-LI cells. These results provide evidence that TRB3 acts as a potent negative regulator of PPAR gamma, a master regulator of adipocyte differentiation, and tightly controls adipogenesis.