Rev-erbα Inhibits Proliferation and Promotes Apoptosis of Preadipocytes through the Agonist GSK4112
Rev-erbα Inhibits Proliferation and Promotes Apoptosis of Preadipocytes through the Agonist GSK4112
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Rev-erbα 通过激动剂 GSK4112 抑制前脂肪细胞的增殖并促进其凋亡
DOI：
10.3390/ijms20184524
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发表时间：
2019-09-02
影响因子：
5.6
通讯作者：
Yang, Gongshe
中科院分区：
文献类型：
--
作者：
Chu, Guiyan;Zhou, Xiaoge;Yang, Gongshe
增殖和凋亡是前脂肪细胞重要的生理过程。Rev-erb alpha是一种生物钟基因，其活性有助于各种细胞中的几种生理过程。以前的研究表明，Rev-erb α促进前脂肪细胞分化，但Rev-erb α对前脂肪细胞增殖和凋亡的作用尚未得到证实。GSK 4112通常用作Rev-erb α的激动剂。在本研究中，我们使用GSK4112通过RT-qPCR、Western blot、细胞计数试剂盒-8（CCK 8）测量、5-乙炔基-2'-脱氧尿苷（EdU）染色、Annexin V-FITC/PI染色和流式细胞术来探讨Rev-erb alpha对前脂肪细胞增殖和凋亡的影响。这些结果表明，GSK4112抑制3T3-L1前脂肪细胞的活力并减少细胞数量。增殖相关基因Cyclin D和经典无翅型（Wnt）信号传导效应因子β-连环蛋白的表达也降低。此外，棕榈酸酯（PA）诱导的细胞凋亡的促进。总的来说，这些结果表明，Rev-erb α在3T3-L1前脂肪细胞的增殖和棕榈酸酯（PA）诱导的凋亡中起作用，因此可能是预防和治疗肥胖及相关疾病的新分子靶点。
Proliferation and apoptosis are important physiological processes of preadipocytes. Rev-erb alpha is a circadian clock gene, and its activity contributes to several physiological processes in various cells. Previous studies demonstrated that Rev-erb alpha promotes preadipocyte differentiation, but a role of Rev-erb alpha on preadipocyte proliferation and apoptosis has not been demonstrated. GSK4112 is often used as an agonist of Rev-erb alpha. In this study, we used GSK4112 to explore the effects of Rev-erb alpha on preadipocyte proliferation and apoptosis by RT-qPCR, Western blot, Cell Counting Kit-8 (CCK8) measurement, 5-Ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/PI staining, and flow cytometry. These results revealed that GSK4112 inhibited the viability of 3T3-L1 preadipocytes and decreased cell numbers. There was also decreased expression of the proliferation-related gene Cyclin D and the canonical Wingless-type (Wnt) signaling effect factor beta-catenin. Furthermore, palmitate (PA)-inducing cell apoptosis was promoted. Overall, these results reveal that Rev-erb alpha plays a role in proliferation and palmitate (PA)-inducing apoptosis of 3T3-L1 preadipocytes, and thus may be a new molecular target in efforts to prevent and treat obesity and related disease.