Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, 22 Xinong Road, Yangling, Shaanxi Province 712100, People's Republic of China.
Mol Biol Rep. 2012 Mar;39(3):3343-54. doi: 10.1007/s11033-011-1104-8. Epub 2011 Jul 6.
Previous report showed that Estrogen related receptor α (ERRα) knockout mice had a significant reduction in adipose tissue deposition. Although it was reported that ERRα could promote adipogenesis in several immortalized preadipocytes cell lines, the mechanism behind which is still unclear to date. Besides, the expression pattern of ERRα in white adipose tissue is rarely examined. Here, we show that the expression of ERRα in primary cultured adipocytes is closely associated with adipogenesis. Besides, we found that peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) play an important role in regulating ERRα-induced adipogenesis. ERRα-induced adipogenesis was greatly attenuated when knocking down PGC-1β expression, while rescued by overexpression of PGC-1β. However, PGC-1β could still promote adipogenesis when suppressing ERRα expression. Furthermore, we demonstrated that ERRα could transcriptionally active PGC-1β expression and then enhance the formation of sterol-regulatory-element-binding protein-1c (SREBP-1c)/PGC-1β complex and peroxisome proliferator-activated receptor-γ (PPARγ)/PGC-1β complex. Taken together, these results indicate that ERRα-induced adipogenesis is triggered by modulating the expression of PGC-1β.
先前的报告表明,雌激素相关受体α(ERRα)敲除小鼠的脂肪组织沉积明显减少。尽管有报道称 ERRα 可以促进几种永生化前体脂肪细胞系的脂肪生成,但迄今为止,其背后的机制仍不清楚。此外,ERRα 在白色脂肪组织中的表达模式很少被研究。在这里,我们发现原代培养脂肪细胞中 ERRα 的表达与脂肪生成密切相关。此外,我们发现过氧化物酶体增殖物激活受体-γ 共激活因子 1β(PGC-1β)在调节 ERRα 诱导的脂肪生成中起着重要作用。当敲低 PGC-1β 的表达时,ERRα 诱导的脂肪生成大大减弱,而过表达 PGC-1β 则可以恢复。然而,当抑制 ERRα 的表达时,PGC-1β 仍然可以促进脂肪生成。此外,我们证明 ERRα 可以转录激活 PGC-1β 的表达,从而增强固醇调节元件结合蛋白-1c(SREBP-1c)/PGC-1β 复合物和过氧化物酶体增殖物激活受体-γ(PPARγ)/PGC-1β 复合物的形成。综上所述,这些结果表明 ERRα 诱导的脂肪生成是通过调节 PGC-1β 的表达来触发的。