Mir193b-365 is essential for brown fat differentiation.
Mir193b-365 is essential for brown fat differentiation.
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DOI：
10.1038/ncb2286
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发表时间：
2011-07-10
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
哺乳动物有两种主要的脂肪。白色脂肪组织（WAT）主要作为甘油三酯储存额外的能量，而棕色脂肪组织（BAT）专门用于燃烧脂质以产生热量和消耗能量，作为抵御寒冷和肥胖的防御。最近的研究表明，体内棕色脂肪细胞由myf5阳性的成肌细胞祖细胞在Prdm16 （PR结构域包含16）的作用下产生。在这里，我们确定了一个棕色脂肪富集的miRNA簇miR-193b-365，作为棕色脂肪发育的关键调节因子。阻断原代棕色前脂肪细胞中的miR-193b和/或miR-365，通过增强Runx1t1（矮子相关转录因子1；易位到1,1）的表达，显著损害棕色脂肪细胞的脂肪生成，而肌源性标志物则被显著诱导。在C2C12成肌细胞中强制表达miR-193b和/或miR-365阻断了整个成肌过程，并且在成脂条件下，miR-193b诱导成肌细胞分化为棕色脂肪细胞。MiR-193b-365被Prdm16部分通过Pparα上调。我们的研究结果表明，miR-193b-365是棕色脂肪分化的重要调节因子，部分是通过抑制肌肉生成来实现的。
Mammals have two principal types of fat. White adipose tissue (WAT) primarily serves to store extra energy as triglycerides, while brown adipose tissue (BAT) is specialized to burn lipids for heat generation and energy expenditure as a defense against cold and obesity . Recent studies demonstrate that brown adipocytes arise in vivo from a Myf5-positive, myoblastic progenitor by the action of Prdm16 (PR domain containing 16). Here, we identified a brown fat-enriched miRNA cluster, miR-193b-365, as a key regulator of brown fat development. Blocking miR-193b and/or miR-365 in primary brown preadipocytes dramatically impaired brown adipocyte adipogenesis by enhancing Runx1t1 (runt-related transcription factor 1; translocated to, 1) expression whereas myogenic markers were significantly induced. Forced expression of miR-193b and/or miR-365 in C2C12 myoblasts blocked the entire program of myogenesis, and, in adipogenic condition, miR-193b induced myoblasts to differentiate into brown adipocytes. MiR-193b-365 was upregulated by Prdm16 partially through Pparα. Our results demonstrate that miR-193b-365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1073/pnas.1010929108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Schulz, Tim J.;Huang, Tian Lian;Tseng, Yu-Hua
通讯作者：
Tseng, Yu-Hua
影响因子：
4.8
作者：
Hamann, A;Flier, JS;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
10.5
作者：
Kajimura, Shingo;Seale, Patrick;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1042/bj20091112
发表时间：
2009-12-14
期刊：
The Biochemical journal
影响因子：
--
作者：
Payne VA;Au WS;Lowe CE;Rahman SM;Friedman JE;O'Rahilly S;Rochford JJ
通讯作者：
Rochford JJ