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Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver

Author

Listed:
  • Hong Chen

    (Huazhong University of Science and Technology)

  • Chong Liu

    (Wuhan University)

  • Qian Wang

    (Huazhong University of Science and Technology)

  • Mingrui Xiong

    (Huazhong University of Science and Technology)

  • Xia Zeng

    (Huazhong University of Science and Technology)

  • Dong Yang

    (Huazhong University of Science and Technology)

  • Yunhao Xie

    (Wuhan University)

  • Hua Su

    (Huazhong University of Science and Technology)

  • Yu Zhang

    (Huazhong University of Science and Technology)

  • Yixue Huang

    (Huazhong University of Science and Technology)

  • Yuchen Chen

    (Huazhong University of Science and Technology)

  • Junqiu Yue

    (Huazhong University of Science and Technology)

  • Chengyu Liu

    (Wuhan Hospital of Traditional and Western Medicine)

  • Shun Wang

    (Wuhan Hospital of Traditional and Western Medicine)

  • Kun Huang

    (Huazhong University of Science and Technology)

  • Ling Zheng

    (Wuhan University
    Wuhan University)

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 Lys310 and Lys330, 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.

Suggested Citation

  • Hong Chen & Chong Liu & Qian Wang & Mingrui Xiong & Xia Zeng & Dong Yang & Yunhao Xie & Hua Su & Yu Zhang & Yixue Huang & Yuchen Chen & Junqiu Yue & Chengyu Liu & Shun Wang & Kun Huang & Ling Zheng, 2022. "Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31476-0
    DOI: 10.1038/s41467-022-31476-0
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    Cited by:

    1. Yangmian Yuan & Yu Fan & Yihao Zhou & Rong Qiu & Wei Kang & Yu Liu & Yuchen Chen & Chenyu Wang & Jiajian Shi & Chengyu Liu & Yangkai Li & Min Wu & Kun Huang & Yong Liu & Ling Zheng, 2023. "Linker histone variant H1.2 is a brake on white adipose tissue browning," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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