Integrative transcriptomics and metabolomics explore the mechanism of kaempferol on improving nonalcoholic steatohepatitis
Integrative transcriptomics and metabolomics explore the mechanism of kaempferol on improving nonalcoholic steatohepatitis
复制标题
综合转录组学和代谢组学探讨山奈酚改善非酒精性脂肪性肝炎的机制。
DOI：
10.1039/d0fo02123g
复制
发表时间：
2020-11-01
期刊：
影响因子：
6.1
通讯作者：
Ji, Guang
中科院分区：
文献类型：
--
作者：
Lu, Yifei;Shao, Mingmei;Ji, Guang
山奈酚已被证实对改善糖尿病和肥胖等代谢性疾病有效。然而，其在非酒精性脂肪性肝炎（NASH）中的作用和机制尚不清楚。我们的目的是确认山奈酚是否可以改善NASH，并找到相应的差异基因和代谢物。转录组学结合代谢组学研究山奈酚治疗高脂肪饮食诱导的NASH小鼠后基因和代谢物表达的变化。结果显示山奈酚可降低血清丙氨酸转氨酶（ALT）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）水平及甘油三酯（TG）、脂滴及肝脏炎症细胞浸润。此外，通过肝脏转录组学鉴定出277个差异表达基因（DEGs），其中最明显的五个差异表达基因是CYP2b9、Cyp4a12b、Mup17、Mup7和Mup16，这表明HFD诱导脂肪酸降解、核糖体以及乙醛酸和二羧酸代谢。鉴定出9种血清代谢物（甲基半胱氨酸、l-色氨酸、肾上腺酸、d-2-羟基戊二酸、酒石酸、对甲酚硫酸盐、l-丙氨酸、l-tryosine和谷氨酸）和3种肝脏差异代谢物（没食子酸、γ-lindenic酸和l-苯丙氨酸），途径主要参与苯丙氨酸、酪氨酸和色氨酸的生物合成；还有苯丙氨酸代谢。整合转录组学和代谢组学分析表明，山奈酚具有改善与能量代谢、脂质代谢、氧化应激和炎症相关途径相关的NASH的能力。本研究为多组学数据整合提供了强有力的手段，揭示了山奈酚的有效治疗方法和生物标志物。
Kaempferol has been confirmed to be effective in improving metabolic diseases such as diabetes and obesity. However, its effect and mechanism in nonalcoholic steatohepatitis (NASH) are unclear. We aim to confirm whether kaempferol could improve NASH and find the corresponding differential genes and metabolites. Transcriptomics combined with metabolomics was used to investigate the alterations in genes and metabolites expression after kaempferol treatment in mice with high-fat-diet-induced NASH. The results showed that kaempferol reduced the level of alanine transaminase (ALT), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in serum and triglyceride (TG), lipid droplets, and inflammatory cell infiltration in liver. Further, 277 differentially expressed genes (DEGs) were identified through liver transcriptomics and the five most obvious DEGs were found to be CYP2b9, Cyp4a12b, Mup17, Mup7, and Mup16, which revealed that HFD induced fatty acid degradation, ribosome, and glyoxylic acid and dicarboxylic acid metabolism. Nine serum metabolites (methylcysteine, l-tryptophan, adrenic acid, d-2-hydroxyglutaric acid, tartaric acid, p-cresol sulfate, l-alanine, l-tryosine, and glutaconic acid) and 3 liver differential metabolites (gallic acid, γ-lindenic acid, and l-phenylalanine) were also identified, while the pathways were mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. Integrating transcriptomics and metabolomics analyses indicated that kaempferol possesses the ability to improve NASH associated with energy metabolism, lipid metabolism, oxidative stress, and inflammation-related pathways. This study provides a powerful means of multiomics data integration and reveals the potent therapy and biomarkers for kaempferol.