State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Department of Animal Science, China Agricultural University, Beijing, 100193, China.
Protein Cell. 2021 Jun;12(6):475-492. doi: 10.1007/s13238-020-00770-2. Epub 2020 Aug 14.
RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.
RNF20 是一种 E3 连接酶，在赖氨酸 120 位（H2Bub）单泛素化组蛋白 H2B 中起关键作用，它参与调节各种细胞过程；然而，其在脂肪细胞中的生理作用仍知之甚少。在这里，我们报道了小鼠脂肪细胞特异性敲除 Rnf20（ASKO）导致进行性脂肪丢失、器官肿大和高胰岛素血症。尽管存在高胰岛素血症的迹象，但年轻和年老的 CD 喂养 ASKO 小鼠表现出正常的胰岛素敏感性和改善的葡萄糖耐量。此外，高脂肪饮食喂养的 ASKO 小鼠发生严重的肝脂肪变性。此外，我们观察到由于棕色脂肪组织（BAT）选择性基因的表达水平降低，包括解偶联蛋白 1（Ucp1），以及线粒体功能受损，ASKO 小鼠对冷环境极为敏感。在 ASKO 小鼠的性腺白色脂肪组织（gWAT）中，过氧化物酶体增殖物激活受体γ（Pparγ）的水平显著降低，表明 Rnf20 通过 Pparγ 调节脂肪生成，至少部分如此。与未经处理的 ASKO 小鼠相比，罗格列酮处理的 ASKO 小鼠的脂肪量增加。总的来说，我们的研究结果说明了 RNF20 在控制白色和棕色脂肪组织发育和生理功能中的关键作用。
