Transcriptional control of brown fat determination by PRDM16
Transcriptional control of brown fat determination by PRDM16
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DOI：
10.1016/j.cmet.2007.06.001
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发表时间：
2007-07-01
期刊：
影响因子：
29
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Seale, Patrick;Kajimura, Shingo;Spiegelman, Bruce M.
棕色脂肪细胞专门用于消耗能量，可以对抗肥胖;然而，它们的决定的转录基础在很大程度上是未知的。我们在这里表明，锌指蛋白PRDM 16是高度富集在棕色脂肪细胞相比，白色脂肪细胞。当在白色脂肪祖细胞中表达时，PRDM 16激活稳健的棕色脂肪表型，包括诱导PGC-1 α、UCP 1和2型脱碘酶（Dio 2）表达以及解偶联呼吸的显著增加。PRDM 16在白色脂肪库中以生理水平的转基因表达刺激棕色脂肪细胞的形成。通过棕色脂肪细胞中的shRNA表达消耗PRDM 16导致棕色特征几乎完全丧失。PRDM 16至少部分地通过直接蛋白结合同时激活PGC-1 α和PGC-1 β来激活棕色脂肪细胞特性。这些数据表明PRDM 16可以控制棕色脂肪命运的测定。
Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1 alpha, UCP1, and type 2 deiodinase (Dio2) expression and a remarkable increase in uncoupled respiration. Transgenic expression of PRDM16 at physiological levels in white fat depots stimulates the formation of brown fat cells. Depletion of PRDM16 through shRNA expression in brown fat cells causes a near total loss of the brown characteristics. PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1 alpha and PGC-1 beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate.