FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2 receptor-Akt signaling pathway.

FAM3A enhances adipogenesis of 3T3-L1 preadipocytes via activation of ATP-P2 receptor-Akt signaling pathway.
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FAM3A 通过激活 ATP-P2 受体-Akt 信号通路增强 3T3-L1 前脂肪细胞的脂肪生成

DOI:
10.18632/oncotarget.17578
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发表时间:
2017-07-11
期刊:
影响因子:
--
通讯作者:
Yang J
Yang J
中科院分区:
其他
文献类型:
--
作者:
Chi Y;Li J;Li N;Chen Z;Ma L;Peng W;Pan X;Li M;Yu W;He X;Geng B;Cui Q;Liu Y;Yang J

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FAM 3A在调节肝脏糖脂代谢和VSMCs增殖中起重要作用。本研究旨在探讨FAM 3A在3 T3-L1前脂肪细胞成脂过程中的作用及其机制。在3 T3-L1前脂肪细胞的脂肪形成过程中,FAM 3A的表达显著增加。FAM 3A过表达促进3 T3-L1前脂肪细胞的脂肪形成,同时增加磷酸化Akt(pAkt)水平,而FAM 3A沉默抑制3 T3-L1前脂肪细胞的脂肪形成,同时降低pAkt水平。此外,FAM 3A沉默降低了3 T3-L1细胞中脂肪因子的表达和分泌。FAM 3A蛋白主要定位于3 T3-L1细胞的线粒体组分和小鼠脂肪组织中。在3 T3-L1前脂肪细胞中,FAM 3A过表达增加,而FAM 3A沉默减少ATP产生。FAM 3A诱导的3 T3-L1前脂肪细胞的脂肪形成被P2受体抑制剂所减弱。在db/db和HFD喂养的肥胖小鼠的白色脂肪组织中,FAM 3A表达降低。罗格列酮给药1个月可上调正常和肥胖小鼠白色脂肪组织中FAM 3A的表达,并增加细胞ATP含量和pAkt水平。FAM 3A通过激活ATP-P2受体-Akt通路促进前脂肪细胞的成脂。在肥胖状态下,脂肪组织中FAM 3A表达的降低在脂肪功能障碍和2型糖尿病的发展中起重要作用。
FAM3A plays important roles in regulating hepatic glucose/lipid metabolism and the proliferation of VSMCs. This study determined the role and mechanism of FAM3A in the adipogenesis of 3T3-L1 preadipocytes. During the adipogenesis of 3T3-L1 preadipocytes, FAM3A expression was significantly increased. FAM3A overexpression enhanced 3T3-L1 preadipocyte adipogenesis with increased phosphorylated Akt (pAkt) level, whereas FAM3A silencing inhibited 3T3-L1 preadipocyte adipogenesis with reduced pAkt level. Moreover, FAM3A silencing reduced the expression and secretion of adipokines in 3T3-L1 cells. FAM3A protein is mainly located in mitochondrial fraction of 3T3-L1 cells and mouse adipose tissue. FAM3A overexpression increased, whereas FAM3A silencing decreased ATP production in 3T3-L1 preadipocytes. FAM3A-induced adipogenesis of 3T3-L1 preadipocytes was blunted by inhibitor of P2 receptor. In white adipose tissues of db/db and HFD-fed obese mice, FAM3A expression was reduced. One-month rosiglitazone administration upregulated FAM3A expression, and increased cellular ATP content and pAkt level in white adipose tissues of normal and obese mice. In conclusion, FAM3A enhances the adipogenesis of preadipocytes by activating ATP-P2 receptor-Akt pathway. Under obese condition, a decrease in FAM3A expression in adipose tissues plays important roles in the development of adipose dysfunction and type 2 diabetes.
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