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Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis
来源: | 作者:pmo597dc1 | 时间 :2018-01-29 | 1046 次浏览 | 分享到:

Cell Metabolism??January 9, 2018
SUMMARY
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16
transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the transcription of transforming growth factor b-dependent pro-fibrosis genes
by recruiting PRDM16 and EHMT1 onto their promoter/ enhancer regions. These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16
complex leads to an improvement in systemic glucose homeostasis.

解读:

这篇论文发现脂肪细胞中存在的GTF2ID1基因能够降低脂肪组织纤维化的程度。小鼠在接受了高脂饮食之后往往会出现肥胖的症状,而研究者们发现通过提高脂肪细胞中上述转录蛋白的表达,能够显着降低脂肪纤维化的程度,以及能够提高葡萄糖代谢的水平。然而,GTFIRD1的缺陷则产生了完全相反的效应,小鼠脂肪组织纤维化程度加重,葡萄糖代谢的通路也受到了阻碍。在人类患者的相关样本中也检测了脂肪组织中GTF2IRD1的表达水平,结果显示,该蛋白的表达量与纤维化程度存在明显的反向相关性。此外,作者还发现该蛋白表达水平越高,患者的体脂分布就越健康,糖尿病的患病风险也越低。这一发现能够帮助鉴定哪些患者更容易出现脂肪组织纤维化的症状,以及筛选能够靶向GTF2IRD1的药物,通过抵抗纤维化的方式缓解糖尿病的发生风险。


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