Protein Arginine Methyltransferase PRMT5 Regulates Fatty Acid Metabolism and Lipid Droplet Biogenesis in White Adipose Tissues,Advanced Science

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Protein Arginine Methyltransferase PRMT5 Regulates Fatty Acid Metabolism and Lipid Droplet Biogenesis in White Adipose Tissues
Advanced Science ( IF 14.3 ) Pub Date : 2020-10-16 , DOI: 10.1002/advs.202002602
Zhihao Jia ₁ , Feng Yue ₁ , Xiyue Chen ₁ , Naagarajan Narayanan _{2,

3} , Jiamin Qiu ₁ , Sabriya A Syed ₄ , Anthony N Imbalzano ₄ , Meng Deng _{2,

3} , Peng Yu _{5,

6} , Changdeng Hu _{7,

8} , Shihuan Kuang _{1,

8}

Affiliation

The protein arginine methyltransferase 5 (PRMT5) is an emerging regulator of cancer and stem cells including adipogenic progenitors. Here, a new physiological role of PRMT5 in adipocytes and systemic metabolism is reported. Conditional knockout mice were generated to ablate the Prmt5 gene specifically in adipocytes (Prmt5^AKO). The Prmt5^AKO mice exhibit sex‐ and depot‐dependent progressive lipodystrophy that is more pronounced in females and in visceral (than subcutaneous) white fat. The lipodystrophy and associated energy imbalance, hyperlipidemia, hepatic steatosis, glucose intolerance, and insulin resistance are exacerbated by high‐fat‐diet. Mechanistically, Prmt5 methylates and releases the transcription elongation factor SPT5 from Berardinelli‐Seip congenital lipodystrophy 2 (Bscl2, encoding Seipin) promoter, and Prmt5^AKO disrupts Seipin‐mediated lipid droplet biogenesis. Prmt5 also methylates Sterol Regulatory Element‐Binding Transcription Factor 1a (SREBP1a) and promotes lipogenic gene expression, and Prmt5^AKO suppresses SREBP1a‐dependent fatty acid metabolic pathways in adipocytes. Thus, PRMT5 plays a critical role in regulating lipid metabolism and lipid droplet biogenesis in adipocytes.

中文翻译：

蛋白质精氨酸甲基转移酶 PRMT5 调节白色脂肪组织中的脂肪酸代谢和脂滴生物发生

蛋白质精氨酸甲基转移酶 5 (PRMT5) 是一种新兴的癌症和干细胞（包括脂肪形成祖细胞）的调节因子。在此，报道了 PRMT5 在脂肪细胞和全身代谢中的新生理作用。生成条件性基因敲除小鼠以特异性消除脂肪细胞中的Prmt5基因（Prmt5 ^AKO）。Prmt5 ^AKO小鼠表现出性别和库依赖性进行性脂肪营养不良，这种情况在雌性和内脏（比皮下）白色脂肪中更为明显。高脂肪饮食会加剧脂肪营养不良和相关的能量失衡、高脂血症、肝脂肪变性、葡萄糖耐受不良和胰岛素抵抗。从机制上讲，Prmt5 甲基化并从 Berardinelli-Seip 先天性脂肪营养不良 2（ Bscl2，编码 Seipin）启动子释放转录延伸因子 SPT5 ，并且 Prmt5 ^AKO破坏 Seipin 介导的脂滴生物合成。Prmt5 还甲基化甾醇调节元件结合转录因子 1a (SREBP1a) 并促进脂肪生成基因表达，Prmt5 ^AKO抑制脂肪细胞中 SREBP1a 依赖性脂肪酸代谢途径。因此，PRMT5 在调节脂肪细胞的脂质代谢和脂滴生物发生中发挥着关键作用。

更新日期：2020-12-03

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