Downregulation of osteopontin inhibits browning of white adipose tissues through PI3K-AKT pathway in C57BL/6 mice
Downregulation of osteopontin inhibits browning of white adipose tissues through PI3K-AKT pathway in C57BL/6 mice
复制标题
在 C57BL/6 小鼠中，骨桥蛋白的下调通过 PI3K-AKT 途径抑制白色脂肪组织的褐变。
DOI：
10.1016/j.ejphar.2019.172822
复制
发表时间：
2020-01-05
影响因子：
5
通讯作者：
Huang, Qiren
中科院分区：
文献类型：
--
作者：
Lu, Yi;Xu, Yuhong;Huang, Qiren
棕色脂肪组织（BAT）在调节能量平衡和对抗肥胖中起着重要作用。因此，增加BAT的丰度和/或激活BAT将是对抗肥胖和肥胖相关疾病的有效且有前景的方法。我们的前期体外实验结果表明，骨桥蛋白（OPN）通过磷脂酰肌醇3激酶（PI 3 K）-AKT通路诱导3 T3-L1细胞棕色脂肪形成。然而，目前尚不清楚OPN是否在体内对动物产生这种作用。因此，本研究通过Ad-GFP-aP 2-OPN-shRNA特异性下调小鼠白色脂肪组织（WAT）中OPN的表达，探讨OPN促褐变的作用机制。我们目前的结果表明，WAT中OPN的下调会加剧肥胖并抑制WAT褐变。此外，免疫组化结果还显示，OPN的下调显著减少了UCP-1、PRDM 16和PGC-1 α的表达和亚细胞定位。Western blotting结果显示PI 3 K、AKT-pS473和PPAR γ的表达水平明显降低。因此，我们得出结论，下调OPN通过抑制PI 3 K-AKT通路介导的PPAR γ表达来抑制WAT的布朗宁。研究结果表明，OPN参与调节WAT-browning，调节其表达将成为对抗肥胖和肥胖相关代谢疾病的潜在策略。
Brown adipose tissue (BAT) plays important roles in regulating energy homeostasis and combating obesity. Accordingly, increasing the abundance and/or activating BAT would be effective and promising approaches to combat obesity and obesity-relative diseases. Our previous data in vitro have shown that osteopontin (OPN) induces the brown adipogenesis in 3T3-L1 cells via a phosphatidylinositol 3 kinase (PI3K)-AKT pathway. However, it is currently unknown whether OPN exerts such an effect on animals in vivo. Therefore, in the study we sought to investigate the pro-browning effects of OPN and to explore its underlying mechanisms by transfecting with Ad-GFP-aP2-OPN-shRNA to specifically down-regulate the OPN of white adipose tissue (WAT) in mice. Our present results show that downregulation of OPN in WAT exacerbates obesity and inhibits WAT-browning. Moreover, immunohistochemical results also exhibit that the downregulation of OPN significantly diminishes the expression and sub-cellular localization of UCP-1, PRDM16 and PGC-1 alpha. Besides, the western blotting results reveal that the expression levels of PI3K, AKT-pS473 and PPAR gamma markedly reduce. Consequently, we conclude that the downregulation of OPN inhibits the browning of WAT through inhibiting the expression of PPAR gamma mediated by the PI3K-AKT pathway. The findings suggest that OPN is involved in regulation of WAT-browning and regulating its expression would become a potential strategy to combat obesity and obesity-relative metabolic diseases.