非酒精性脂肪性肝病多组学研究现状

段明秀; 陈新利; 常伟宇; 杨媛; 杨仕琦; 吴晖

doi:10.12449/JCH240626

非酒精性脂肪性肝病多组学研究现状

DOI: 10.12449/JCH240626

昆明医科大学第一附属医院临床药学中心，昆明 650000

基金项目:

云南省应用基础研究专项项目 (202301AT070152)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：段明秀负责课题设计，资料分析，撰写论文；吴晖、陈新利、常伟宇参与收集数据，修改论文；杨媛、杨仕琦负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
吴晖， kyz_ggyx@163.com （ORCID： 0009-0003-5966-3570）

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出版历程
- 收稿日期: 2023-08-24
- 录用日期: 2023-11-24
- 出版日期: 2024-06-25

Advances in the multi-omics research on nonalcoholic fatty liver disease

Centre for Clinical Pharmacy，The First Affiliated Hospital of Kunming Medical University，Kunming 650000，China

Research funding:

Yunnan Province Applied Basic Research Special Project (202301AT070152)

More Information

Corresponding author: WU Hui， kyz_ggyx@163.com （ORCID： 0009-0003-5966-3570）

摘要

摘要: 非酒精性脂肪性肝病（NAFLD）在全球范围内患病率高达30%，严重影响人类健康并构成公共卫生负担。由于该病难以诊断和监控，因此，识别潜在的药物靶点和生物标志物具有重要价值，多组学技术在探索NAFLD早期诊断标志物、治疗靶点、疗效和预后评估方面具有广阔的前景。本文对近年来多组学技术在NAFLD中领域的研究进展进行综述，以期为NAFLD的防治提供更为丰富的理论依据和新的策略。
- 非酒精性脂肪性肝病 /
- 基因组学 /
- 蛋白质组学 /
- 代谢组学 /
- 胃肠道微生物组
Abstract: The prevalence rate of nonalcoholic fatty liver disease （NAFLD） reaches up to 30% around the world， and the disease has a serious impact on human health and constitutes a public health burden. Due to difficulties in the diagnosis and monitoring of NAFLD， it is important to identify potential drug targets and biomarkers， and multi-omics techniques hold great promise in the search for early diagnostic markers， therapeutic targets， and outcome and prognostic assessment of NAFLD. This article reviews the research advances in multi-omics techniques in the field of NAFLD in recent years， in order to provide a richer theoretical basis and new strategies for the prevention and treatment of NAFLD.
- Non-alcoholic Fatty Liver Disease /
- Genomics /
- Proteomics /
- Metabolomics /
- Gastrointestinal Microbiome

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图 1 NAFLD多组学研究

Figure 1. Multi-omics study of NAFLD

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表 1 NAFLD的代谢组学研究

Table 1. Metabolomics studies in NAFLD

样本类型	组别	重要代谢物	涉及代谢通路	参考文献
血清	NAFLD组（n=157），NASH组（n=138），健康对照组（n=66）	脂肪酸；甘油酯；甘油磷脂，溶血磷脂酸、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺、磷脂酰胆碱、磷脂酰乙醇胺和磷脂酰肌醇；鞘脂	脂质代谢	［53］
血清	NAFLD组（n=144），健康对照组（n=368）	s-腺苷蛋氨酸、s-腺苷同型半胱氨酸和同型半胱氨酸	氨基酸代谢、脂质代谢	［56］
血浆	NAFLD组（n=132），健康对照组（n=42）	磷脂酰胆碱、溶血磷脂酰乙醇胺、磷脂酰胆碱、天冬氨酸转氨酶、丙氨酸转氨酶、γ-谷氨酰转肽酶、白蛋白、总胆红素、甘油三酯、总胆固醇、低密度脂蛋白、胆碱酯酶、透明质酸、C反应蛋白、铁蛋白	磷脂酰胆碱、胆汁酸途径、烟酸和烟酰胺途径、磷脂酰肌醇和三羧酸循环	［57］
血浆	NAFLD组（n=427）	5-羟廿碳四烯酸，7，17-二氢吡啶二羧酸，肾上腺酸，花生四烯酸，二十碳五烯酸，16-羟基二十二碳六烯酸，9-羟基十八碳二烯酸		［58］
血清	NAFLD组（n=627）	2-羟基丁酸、3-羟基丁酸、柠檬酸、异亮氨酸、赖氨酸、油酸、3-OH-苯甲酸、5-OH-1H-吲哚-3-乙酸、吲哚-3-乳酸		［59］
尿液	NASH组（男68例，女65例）	高丙二酸乙酯、β-羟基丁酸、乙基丙二酸酯、硫酸盐水平、高甲氨基谷氨酸、对羟苯乳酸、琥珀酸盐、甲酰亚胺谷氨酸酯、香草扁桃酸酯、吡啶甲酸酯	酪氨酸分解代谢	［60］
尿液	NAFLD组（n=33），NASH组（n=45），健康对照组（n=30）	氨基酸代谢物、瓜氨酸、精氨酸、缬氨酸、吲哚乙酸以及葡萄糖和葡萄糖酸、次黄嘌呤、黄嘌呤和肉碱	脂质过氧化和氧化应激、氨基酸代谢和戊糖磷酸途径	［61］

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表 2 NAFLD的代谢靶点

Table 2. Metabolic targets of NAFLD

靶点	机制	参考文献
抑制CD36棕榈酰化	激活AMPK改善脂质积累，抑制JNK缓解炎症反应	［64］
胆汁酸受体法尼酯X受体、CYP450酶、PPAR、ChREBP、JNK	负调节胆汁酸合成，减少肝脏和肝外组织的糖异生、脂肪生成和脂肪变性、氧化应激、胰岛素抵抗和脂肪酸的调节	［65］
线粒体丙酮酸载体、FFA、ACC	线粒体电子传递链、线粒体β-氧化减少、活性氧过度产生和脂质过氧化	［66］
法尼酯X受体激动剂	反馈调节胆汁酸合成、调节糖脂代谢、调节肝脏炎症和纤维化	［67］

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