肾
内分泌学
丝氨酸
内科学
脱甲基酶
脂肪肝
生物
医学
酶
组蛋白
生物化学
疾病
基因
作者
Hong Chen,Chong Liu,Qian Wang,Mingrui Xiong,Xianlu Zeng,Dong Yang,Yunhao Xie,Hua Su,Yu Zhang,Yixue Huang,Yu‐Chen Chen,Junqiu Yue,Chengyu Liu,Shun Wang,Kun Huang,Ling Zheng
标识
DOI:10.1038/s41467-022-31476-0
摘要
Abstract Global obesity epidemics impacts human health and causes obesity-related illnesses, including the obesity-related kidney and liver diseases. UTX, a histone H3K27 demethylase, plays important roles in development and differentiation. Here we show that kidney-specific knockout Utx inhibits high-fat diet induced lipid accumulation in the kidney and liver via upregulating circulating serine levels. Mechanistically, UTX recruits E3 ligase RNF114 to ubiquitinate phosphoglycerate dehydrogenase, the rate limiting enzyme for de novo serine synthesis, at Lys 310 and Lys 330 , which leads to its degradation, and thus suppresses renal and circulating serine levels. Consistently, phosphoglycerate dehydrogenase and serine levels are markedly downregulated in human subjects with diabetic kidney disease or obesity-related renal dysfunction. Notably, oral administration of serine ameliorates high-fat diet induced fatty liver and renal dysfunction, suggesting a potential approach against obesity related metabolic disorders. Together, our results reveal a metabolic homeostasis regulation mediated by a renal UTX-PHGDH-serine axis.
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