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

被引：3

作者：

Zhu, Ya-Ling ^{[1
,2
]}

Meng, Lei-Lei ^{[1
]}

Ma, Jin-Hu ^{[1
]}

Yuan, Xin ^{[1
]}

Chen, Shu-Wen ^{[1
]}

Yi, Xin-Rui ^{[1
]}

Li, Xin-Yu ^{[1
]}

Wang, Yi ^{[1
]}

Targ, Yun-Shu ^{[1
,2
]}

Xue, Min ^{[1
]}

Zhu, Mei-Zi ^{[1
]}

Peng, Jin ^{[1
]}

Lu, Xue-Jin ^{[1
]}

Huang, Jian-Zhen ^{[4
]}

Song, Zi-Chen ^{[1
]}

Wu, Chong ^{[1
]}

Zheng, Ke-Zhong ^{[3
]}

Dai, Qing-Qing ^{[3
]}

Huang, Fan ^{[3
]}

Fang, Hao-Shu ^{[1
,2
]}

机构：

[1] Anhui Med Univ, Dept Pathophysiol, Hefei 230032, Anhui, Peoples R China

[2] Anhui Med Univ, Lab Anim Res Ctr, Sch Basic Med Sci, Hefei 230032, Anhui, Peoples R China

[3] Anhui Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China

[4] Jiangxi Agr Univ, Coll Anim Sci & Technol, Nanchang 330045, Jiangxi, Peoples R China

来源：

ZOOLOGICAL RESEARCH | 2024年 / 45卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Non-alcoholic fatty liver disease; C/EBP beta; Lipopolysaccharide-binding protein; Integrative analysis; Enhancer; LIPOPOLYSACCHARIDE-BINDING PROTEIN; TRANSCRIPTION; SEQ;

D O I：

10.24272/j.issn.2095-8137.2023.022

中图分类号：

Q95 [动物学];

学科分类号：

071002 ;

摘要：

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 beta (C/EBP beta) 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/EBP beta and functional gene SCD as potential regulators and therapeutic targets.

引用

页码：79 / 94

页数：16

共 1 条

[1] The Hexane Fraction of Cyperus rotundus Prevents Non-Alcoholic Fatty Liver Disease Through the Inhibition of Liver X Receptor α-Mediated Activation of Sterol Regulatory Element Binding Protein-1c
Oh, Gyun-Sik
Yoon, Jin
Lee, Gang Gu
Kwak, Jong Hwan
Kim, Seung-Whan
AMERICAN JOURNAL OF CHINESE MEDICINE, 2015, 43 (03): : 477 - 494

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