Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. Recent technological advances, combined with OMICs experiments and explorations involving different biological samples, have uncovered vital aspects of NAFLD biology. In this review, we summarize recent work by our group and others that expands what is known about the role of lipidome in NAFLD pathogenesis. We discuss how pathway and enrichment analyses were performed by integrating a list of query metabolites derived from text-mining existing NAFLD-lipidomics studies, resulting in the identification of nine KEGG dysregulated pathways, including biosynthesis of unsaturated fatty acids, butanoate metabolism, synthesis and degradation of ketone bodies, sphingolipid, arachidonic acid and pyruvate metabolism, and numerous nonsteroidal anti-inflammatory drug pathways predicted from The Small Molecule Pathway Database. We also summarize an integrated pathway-level analysis of genes and lipid-related metabolites associated with NAFLD, which shows overrepresentation of signal transduction, selenium micronutrient network, Class A/1Rhodopsin-like receptors and GPCR ligand binding, and GPCR-downstream signaling. Generated gene-metabolite-disease interaction networks indicate that NAFLD and arterial hypertension are interlinked by molecular signatures. Finally, we discuss how mining pathways and associations among metabolites, lipids, genes, and proteins can be exploited to infer networks and potential pharmacological targets and how lipidomic studies may provide insight into the interrelationships among metabolite clusters thatmodify NAFLD biology, genetic susceptibility, diet, and the gut microbiome.

中文翻译：

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非酒精性脂肪肝疾病中的脂质组：可行的目标。


非酒精性脂肪肝病（NAFLD）已成为最常见的慢性肝病。最近的技术进步，结合 OMIC 实验和涉及不同生物样本的探索，揭示了 NAFLD 生物学的重要方面。在这篇综述中，我们总结了我们小组和其他人最近的工作，扩展了脂质组在 NAFLD 发病机制中的作用的了解。我们讨论了如何通过整合从文本挖掘现有 NAFLD 脂质组学研究中衍生的查询代谢物列表来进行通路和富集分析，从而识别出九个 KEGG 失调通路，包括不饱和脂肪酸的生物合成、丁酸代谢、合成和降解酮体、鞘脂、花生四烯酸和丙酮酸代谢，以及小分子途径数据库预测的许多非甾体抗炎药物途径。我们还总结了与 NAFLD 相关的基因和脂质相关代谢物的综合途径水平分析，显示信号转导、硒微量营养素网络、A/1 类视紫红质样受体和 GPCR 配体结合以及 GPCR 下游信号传导的过度表达。生成的基因-代谢物-疾病相互作用网络表明 NAFLD 和动脉高血压通过分子特征相互关联。最后，我们讨论了如何利用代谢物、脂质、基因和蛋白质之间的挖掘途径和关联来推断网络和潜在的药理学靶标，以及脂质组学研究如何深入了解改变 NAFLD 生物学、遗传易感性、饮食、代谢物簇之间的相互关系。和肠道微生物组。