PRDM16对棕色脂肪决定的转录调控。
Transcriptional control of brown fat determination by PRDM16.
作者信息
Seale Patrick, Kajimura Shingo, Yang Wenli, Chin Sherry, Rohas Lindsay M, Uldry Marc, Tavernier Geneviève, Langin Dominique, Spiegelman Bruce M
机构信息
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.
出版信息
Cell Metab. 2007 Jul;6(1):38-54. doi: 10.1016/j.cmet.2007.06.001.
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-1alpha, 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-1alpha and PGC-1beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate.
棕色脂肪细胞专门用于消耗能量，能够对抗肥胖；然而，其分化的转录基础在很大程度上尚不清楚。我们在此表明，与白色脂肪细胞相比，锌指蛋白PRDM16在棕色脂肪细胞中高度富集。当在白色脂肪细胞祖细胞中表达时，PRDM16激活强大的棕色脂肪表型，包括诱导PGC-1α、UCP1和2型脱碘酶（Dio2）表达以及解偶联呼吸显著增加。PRDM16在白色脂肪库中的生理水平转基因表达刺激棕色脂肪细胞的形成。通过在棕色脂肪细胞中表达shRNA来消耗PRDM16会导致棕色特征几乎完全丧失。PRDM16至少部分地通过直接蛋白质结合同时激活PGC-1α和PGC-1β来激活棕色脂肪细胞特性。这些数据表明PRDM16可以控制棕色脂肪命运的分化。
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