Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nat Cell Biol. 2011 Jul 10;13(8):958-65. doi: 10.1038/ncb2286.
Mammals have two principal types of fat. White adipose tissue primarily serves to store extra energy as triglycerides, whereas brown adipose tissue is specialized to burn lipids for heat generation and energy expenditure as a defence against cold and obesity. Recent studies have demonstrated 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 markedly 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 Mir193b and/or Mir365 in C2C12 myoblasts blocked the entire programme of myogenesis, and, in adipogenic conditions, miR-193b induced myoblasts to differentiate into brown adipocytes. Mir193b-365 was upregulated by Prdm16 partially through Pparα. Our results demonstrate that Mir193b-365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis.
哺乳动物有两种主要类型的脂肪。白色脂肪组织主要用作甘油三酯的额外能量储存，而棕色脂肪组织则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机制。最近的研究表明，棕色脂肪细胞是由 Myf5 阳性的成肌细胞前体通过 Prdm16（富含 PR 域的 16）的作用在体内产生的。在这里，我们确定了一个富含棕色脂肪的 miRNA 簇 MiR-193b-365，作为棕色脂肪发育的关键调节因子。在原代棕色前体脂肪细胞中阻断 miR-193b 和/或 miR-365 显著通过增强 Runx1t1（runt 相关转录因子 1；易位到 1）的表达来损害棕色脂肪细胞的脂肪生成，而肌肉标志物的表达则显著升高。在 C2C12 成肌细胞中强制表达 Mir193b 和/或 Mir365 阻断了整个成肌过程，并且在脂肪生成条件下，miR-193b 诱导成肌细胞分化为棕色脂肪细胞。Mir193b-365 部分通过 Pparα 被 Prdm16 上调。我们的结果表明，Mir193b-365 作为棕色脂肪分化的必需调节剂，部分通过抑制成肌作用来发挥作用。
