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

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 di...

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Autores principales: Chen, Hong, Liu, Chong, Wang, Qian, Xiong, Mingrui, Zeng, Xia, Yang, Dong, Xie, Yunhao, Su, Hua, Zhang, Yu, Huang, Yixue, Chen, Yuchen, Yue, Junqiu, Liu, Chengyu, Wang, Shun, Huang, Kun, Zheng, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253056/
https://www.ncbi.nlm.nih.gov/pubmed/35788583
http://dx.doi.org/10.1038/s41467-022-31476-0
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author Chen, Hong
Liu, Chong
Wang, Qian
Xiong, Mingrui
Zeng, Xia
Yang, Dong
Xie, Yunhao
Su, Hua
Zhang, Yu
Huang, Yixue
Chen, Yuchen
Yue, Junqiu
Liu, Chengyu
Wang, Shun
Huang, Kun
Zheng, Ling
author_facet Chen, Hong
Liu, Chong
Wang, Qian
Xiong, Mingrui
Zeng, Xia
Yang, Dong
Xie, Yunhao
Su, Hua
Zhang, Yu
Huang, Yixue
Chen, Yuchen
Yue, Junqiu
Liu, Chengyu
Wang, Shun
Huang, Kun
Zheng, Ling
author_sort Chen, Hong
collection PubMed
description 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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spelling pubmed-92530562022-07-06 Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver Chen, Hong Liu, Chong Wang, Qian Xiong, Mingrui Zeng, Xia Yang, Dong Xie, Yunhao Su, Hua Zhang, Yu Huang, Yixue Chen, Yuchen Yue, Junqiu Liu, Chengyu Wang, Shun Huang, Kun Zheng, Ling Nat Commun Article 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. Nature Publishing Group UK 2022-07-04 /pmc/articles/PMC9253056/ /pubmed/35788583 http://dx.doi.org/10.1038/s41467-022-31476-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chen, Hong
Liu, Chong
Wang, Qian
Xiong, Mingrui
Zeng, Xia
Yang, Dong
Xie, Yunhao
Su, Hua
Zhang, Yu
Huang, Yixue
Chen, Yuchen
Yue, Junqiu
Liu, Chengyu
Wang, Shun
Huang, Kun
Zheng, Ling
Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver
title Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver
title_full Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver
title_fullStr Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver
title_full_unstemmed Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver
title_short Renal UTX-PHGDH-serine axis regulates metabolic disorders in the kidney and liver
title_sort renal utx-phgdh-serine axis regulates metabolic disorders in the kidney and liver
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253056/
https://www.ncbi.nlm.nih.gov/pubmed/35788583
http://dx.doi.org/10.1038/s41467-022-31476-0
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