Volume 45 Issue 1
Jan.  2024
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Ya-Ling Zhu, Lei-Lei Meng, Jin-Hu Ma, Xin Yuan, Shu-Wen Chen, Xin-Rui Yi, Xin-Yu Li, Yi Wang, Yun-Shu Tang, Min Xue, Mei-Zi Zhu, Jin Peng, Xue-Jin Lu, Jian-Zhen Huang, Zi-Chen Song, Chong Wu, Ke-Zhong Zheng, Qing-Qing Dai, Fan Huang, Hao-Shu Fang. Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease. Zoological Research, 2024, 45(1): 79-94. doi: 10.24272/j.issn.2095-8137.2023.022
Citation: Ya-Ling Zhu, Lei-Lei Meng, Jin-Hu Ma, Xin Yuan, Shu-Wen Chen, Xin-Rui Yi, Xin-Yu Li, Yi Wang, Yun-Shu Tang, Min Xue, Mei-Zi Zhu, Jin Peng, Xue-Jin Lu, Jian-Zhen Huang, Zi-Chen Song, Chong Wu, Ke-Zhong Zheng, Qing-Qing Dai, Fan Huang, Hao-Shu Fang. Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease. Zoological Research, 2024, 45(1): 79-94. doi: 10.24272/j.issn.2095-8137.2023.022

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

doi: 10.24272/j.issn.2095-8137.2023.022
The raw data reported in this paper were deposited in the National Center for Biotechnology Information Sequence Read Archive (NCBI SRA: PRJNA1044849), National Genomics Data Center (GSA: PRJCA017968 and PRJCA002667), and Science Data Bank (DOI:10.57760/sciencedb.09322). All data that support the findings of this study are available from the corresponding authors upon request.
The authors declare they have no competing interests.
H.S.F. and F.H. designed the experiments. Y.L.Z., L.L.M., and J.H.M. performed the experiments and completed the manuscript. X.Y., Y.S.T., M.X., and S.W.C. performed the cell experiments. X.R.Y. and X.Y.L. preformed animal experiments. Y.W. and M.Z.Z. analyzed the H3K27ac ChIP-Seq and RNA-Seq data. J.P. and X.J.L. conducted the core transcription factor prediction. J.Z.H. conducted the integrative ChIP-Seq and RNA-Seq analyses. Z.C.S., C.W., K.Z.Z., and Q.Q.D. analyzed most of the experimental data. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work
Funds:  This study was supported by the National Natural Science Foundation of China (81971875, 82300661), Natural Science Foundation of Anhui province (2308085QH246), Natural Science Foundation of the Anhui Higher Education Institutions (KJ2021A0205), Basic and Clinical Cooperative Research Program of Anhui Medical University (2019xkjT002, 2019xkjT022, 2022xkjT013), Talent Training Program, School of Basic Medical Sciences, Anhui Medical University (2022YPJH102), and National College Students Innovation and Entrepreneurship Training Program of China (202210366024)
More Information
  • Non-alcoholic fatty liver disease (NAFLD) is associated with mutations in lipopolysaccharide-binding protein (LBP), but the underlying epigenetic mechanisms remain understudied. Herein, LBP-/- rats with NAFLD were established and used to conduct integrative targeting-active enhancer histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency. Notably, LBP-/- reduced the inflammatory response but markedly aggravated high-fat diet (HFD)-induced NAFLD in rats, with pronounced alterations in the histone acetylome and regulatory transcriptome. In total, 1 128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type (WT) and LBP-/- NAFLD rats. Based on integrative analysis, CCAAT/enhancer-binding protein β (C/EBPβ) was identified as a pivotal transcription factor (TF) and contributor to dysregulated histone acetylome H3K27ac, and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD. This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβ and functional gene SCD as potential regulators and therapeutic targets.
  • The raw data reported in this paper were deposited in the National Center for Biotechnology Information Sequence Read Archive (NCBI SRA: PRJNA1044849), National Genomics Data Center (GSA: PRJCA017968 and PRJCA002667), and Science Data Bank (DOI:10.57760/sciencedb.09322). All data that support the findings of this study are available from the corresponding authors upon request.
    The authors declare they have no competing interests.
    H.S.F. and F.H. designed the experiments. Y.L.Z., L.L.M., and J.H.M. performed the experiments and completed the manuscript. X.Y., Y.S.T., M.X., and S.W.C. performed the cell experiments. X.R.Y. and X.Y.L. preformed animal experiments. Y.W. and M.Z.Z. analyzed the H3K27ac ChIP-Seq and RNA-Seq data. J.P. and X.J.L. conducted the core transcription factor prediction. J.Z.H. conducted the integrative ChIP-Seq and RNA-Seq analyses. Z.C.S., C.W., K.Z.Z., and Q.Q.D. analyzed most of the experimental data. All authors read and approved the final version of the manuscript.
    #Authors contributed equally to this work
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