蛋白质精氨酸甲基转移酶5
甾醇调节元件结合蛋白
脂滴
脂质代谢
白色脂肪组织
内分泌学
内科学
脂肪营养不良
生物
脂滴包被蛋白
脂毒性
脂肪生成
脂肪组织
化学
脂肪细胞
细胞生物学
胰岛素抵抗
甲基转移酶
生物化学
胆固醇
甾醇
医学
胰岛素
免疫学
基因
人类免疫缺陷病毒(HIV)
抗逆转录病毒疗法
病毒载量
甲基化
作者
Zhihao Jia,Feng Yue,Libin Chen,Naagarajan Narayanan,Jiamin Qiu,Sabriya A. Syed,Anthony N. Imbalzano,Meng Deng,Peng Yu,Chang‐Deng Hu,Shihuan Kuang
标识
DOI:10.1002/advs.202002602
摘要
Abstract 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.
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