MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade.
MicroRNA-146b promotes adipogenesis by suppressing the SIRT1-FOXO1 cascade.
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DOI：
10.1002/emmm.201302647
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发表时间：
2013-10
影响因子：
11.1
通讯作者：
Ha, Tae Youl
中科院分区：
文献类型：
--
作者：
Ahn, Jiyun;Lee, Hyunjung;Jung, Chang Hwa;Jeon, Tae Il;Ha, Tae Youl
Sirtuin 1（SIRT 1）在维持代谢稳态和促进白色脂肪组织中的脂肪动员中起关键作用。然而，SIRT 1在脂肪形成过程中的调节，特别是通过microRNA，仍然不清楚。我们观察到miR-146 b的表达在3 T3-L1细胞的脂肪形成过程中显著增加。通过过表达miR-146 b诱导3 T3-L1分化。相反，抑制miR-146 b会降低脂肪细胞分化。基于生物信息学的研究表明，SIRT 1是miR-146 b的靶点。进一步的分析证实SIRT 1受miR-146 b负调控。我们还观察到miR-146 b直接与SIRT 1的3′-非翻译区结合，并通过SIRT 1下调来抑制脂肪形成。miR-146 b/SIRT 1轴通过增加叉头框O 1（FOXO 1）的乙酰化来介导脂肪形成。在饮食诱导和遗传性肥胖小鼠的脂肪组织中，miR-146 b的表达增加，SIRT 1 mRNA随后减少。此外，通过锁核酸miR-146 b的miR-146 b的体内敲低显著降低了体重和脂肪体积，这与SIRT 1的上调和随后的FOXO 1的乙酰化一致。因此，miR-146 b/SIRT 1通路可能成为肥胖预防和治疗的潜在靶点。
Sirtuin 1 (SIRT1) plays a critical role in the maintenance of metabolic homeostasis and promotes fat mobilization in white adipose tissue. However, regulation of SIRT1 during adipogenesis, particularly through microRNAs, remains unclear. We observed that miR-146b expression was markedly increased during adipogenesis in 3T3-L1 cells. Differentiation of 3T3-L1 was induced by overexpression of miR-146b. Conversely, inhibition of miR-146b decreased adipocyte differentiation. Bioinformatics-based studies suggested that SIRT1 is a target of miR-146b. Further analysis confirmed that SIRT1 was negatively regulated by miR-146b. We also observed that miR-146b bound directly to the 3′-untranslated region of SIRT1 and inhibited adipogenesis through SIRT1 downregulation. The miR-146b/SIRT1 axis mediates adipogenesis through increased acetylation of forkhead box O1 (FOXO1). Expression of miR-146b was increased and SIRT1 mRNA subsequently decreased in the adipose tissues of diet-induced and genetically obese mice. Furthermore, in vivo knockdown of miR-146b by a locked nucleic acid miR-146b antagomir significantly reduced body weight and fat volume in accordance with upregulation of SIRT1 and subsequent acetylation of FOXO1. Therefore, the miR-146b/SIRT1 pathway could be a potential target for obesity prevention and treatment.
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影响因子：
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