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. 2022 Jul 4;13:3835. doi: 10.1038/s41467-022-31476-0

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© The Author(s) 2022

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/.

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Fig. 6 — a–c UTX knockout prevented PA-induced lipid accumulation in HK-2 cells. Oil Red O staining (a), TG level (b) and PHGDH level (c) in UTX knockout HK-2 cells with or without PA stress. b n = 3 biological samples (mean ± SD), ^***P_{TG (Ctrl+CT vs Ctrl+PA)} < 0.0001; ^***P_{TG (Ctrl+PA vs UTX KO+PA)} < 0.0001 (one-way ANOVA); (c) n = 2 biological samples per group. d–g UTX overexpression exacerbated PA-induced lipid accumulation in HK-2 cells. Oil Red O staining (d), TG level (e), PHGDH level (f) and transcriptional levels of TG synthesis/lipid storage related genes (g) in UTX overexpressing HK-2 cells. e, g n = 3 biological samples (mean ± SD), ^**P_{TG (Vec+CT vs Vec+PA)} = 0.0063, ^*P_{TG (Vec+PA vs UTX+PA)} = 0.0119; ^**P_{MOGAT1(Vec+CT vs Vec+PA)} = 0.0033, ^***P_{MOGAT1(Vec+PA vs UTX+PA)} = 0.0009; ^*P_{GPAM (Vec+CT vs Vec+PA)} = 0.0293; ^**P_{CIDEA (Vec+CT vs Vec+PA)} = 0.0038, ^***P_{CIDEA (Vec+PA vs UTX+PA)} = 0.0009; ^***P_{CIDEC (Vec+CT vs Vec+PA)} = 0.0009, ^**P_{CIDEC (Vec+PA vs UTX+PA)} = 0.0076 (one-way ANOVA); (f) n = 2 biological samples per group. h–k PHGDH knockout aggravated PA-induced lipid accumulation and reduced cellular serine/glycine levels in HK-2 cells. TG level (h), transcriptional levels of TG synthesis/storage related genes (i), Nile Red staining (j) and cellular serine (k, top) or glycine (k, bottom) level in PHGDH knockout HK-2 cells. Scale bar, 50 μm. h–j n = 3 biological samples per group, (k) n = 6 biological samples per group (mean ± SD). ^***P_{TG (Ctrl+CT vs Ctrl+PA)} = 0.0006, ^***P_{TG (Ctrl+PA vs PHGDH KO1+PA)} < 0.0001, ^***P_{TG (Ctrl+PA vs PHGDH KO2+PA)} < 0.0001; ^*P_{MOGAT1 (Ctrl+CT vs Ctrl+PA)} = 0.0351, ^*P_{MOGAT1(Ctrl+PA vs PHGDH KO1+PA)} = 0.0408, ^**P_{MOGAT1 (Ctrl+PA vs PHGDH KO2+PA)} = 0.0034; ^*P_{CIDEA(Ctrl+CT vs Ctrl+PA)} = 0.0230, ^*P_{CIDEA (Ctrl+PA vs PHGDH KO1+PA)} = 0.0495, ^*P_{CIDEA (Ctrl+PA vs PHGDH KO2+PA)} = 0.0289; ^*P_{CIDEC (Ctrl+CT vs Ctrl+PA)} = 0.0158, ^**P_{CIDEC (Ctrl+PA vs PHGDH KO1+PA)} = 0.0092, ^***P_{CIDEC (Ctrl+PA vs PHGDH KO2+PA)} = 0.0002; ^***P_{serine (Ctrl+CT vs Ctrl+PA)} < 0.0001, ^**P_{serine (Ctrl+PA vs PHGDH KO+PA)} = 0.0036; ^***P_glycine _{(Ctrl+CT vs Ctrl+PA)} < 0.0001, ^*P_{glycine (Ctrl+PA vs PHGDH KO+PA)} = 0.0101 (one-way ANOVA). a–k at least three independent experiments were performed and similar results were obtained. Source data are provided in the Source Data file.