Adipose tissue is the key organ coordinating whole-body energy homeostasis. Although it has been reported that ring finger protein 20 (RNF20) regulates lipid metabolism in the liver and kidney, the roles of RNF20 in adipose tissue have not been explored. Here, we demonstrate that RNF20 promotes adipogenesis by potentiating the transcriptional activity of peroxisome proliferator–activated receptor-γ (PPARγ). Under normal chow diet feeding, Rnf20 defective (Rnf20+/−) mice exhibited reduced fat mass with smaller adipocytes compared with wild-type littermates. In addition, high-fat diet–fed Rnf20+/− mice alleviated systemic insulin resistance accompanied by a reduced expansion of fat tissue. Quantitative proteomic analyses revealed significantly decreased levels of PPARγ target proteins in adipose tissue of Rnf20+/− mice. Mechanistically, RNF20 promoted proteasomal degradation of nuclear corepressor 1 (NCoR1), which led to stimulation of the transcriptional activity of PPARγ. Collectively, these data suggest that RNF20-NCoR1 is a novel axis in adipocyte biology through fine-tuning the transcriptional activity of PPARγ.

中文翻译：

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RNF20 通过促进脂肪细胞中的 NCoR1 降解作为 PPARγ 的转录辅激活剂

脂肪组织是协调全身能量稳态的关键器官。尽管有报道称无名指蛋白 20 (RNF20) 可调节肝脏和肾脏中的脂质代谢，但尚未探索 RNF20 在脂肪组织中的作用。在这里，我们证明 RNF20 通过增强过氧化物酶体增殖物激活受体-γ（PPARγ）的转录活性来促进脂肪生成。在正常饲料喂养下，与野生型同窝仔畜相比，Rnf20 缺陷 (Rnf20+/-) 小鼠的脂肪量减少，脂肪细胞更小。此外，高脂肪饮食喂养的 Rnf20+/- 小鼠减轻了全身胰岛素抵抗，同时减少了脂肪组织的扩张。定量蛋白质组学分析显示，Rnf20+/- 小鼠脂肪组织中 PPARγ 靶蛋白的水平显着降低。从机制上讲，RNF20 促进核辅抑制因子 1 (NCoR1) 的蛋白酶体降解，从而刺激 PPARγ 的转录活性。总的来说，这些数据表明 RNF20-NCoR1 是脂肪细胞生物学中的一个新轴，通过微调 PPARγ 的转录活性。