Research Institute for Environment and Health, School of Emergency Management, Nanjing University of Information Science and Technology, Nanjing 210044, China.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Nutrients. 2023 Feb 14;15(4):948. doi: 10.3390/nu15040948.
Nonalcoholic fatty liver disease (NAFLD) is considered the most prevalent chronic liver disease, but the understanding of the mechanism of NAFLD is still limited. The aim of our study was to explore hub lncRNAs and mRNAs and pathological processes in high-fat diet (HFD)-induced and lycopene-intervened liver steatosis. We analyzed the gene profiles in the GSE146627 dataset from the Gene Expression Omnibus (GEO) database to identify differentially expressed lncRNAs and mRNAs, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for functional enrichment analysis. We found that the turquoise, blue, brown, yellow, green, and black modules were significantly correlated with NAFLD. Functional enrichment analysis revealed that some hub lncRNAs (Smarca2, Tacc1, Flywch1, and Mef2c) might be involved in the regulation of the inflammatory and metabolic pathways (such as TNF signaling, metabolic, mTOR signaling, MAPK signaling, and p53 signaling pathways) in NAFLD. The establishment of an NAFLD mouse model confirmed that lycopene supply attenuated hepatic steatosis in HFD-induced NAFLD. Our analysis revealed that the inflammatory and metabolic pathways may be crucially involved in the pathogenesis of NAFLD, and hub lncRNAs provide novel biomarkers, therapeutic ideas, and targets for NAFLD. Moreover, lycopene has the potential to be a phytochemical for the prevention of HFD-induced liver steatosis.
非酒精性脂肪性肝病 (NAFLD) 被认为是最常见的慢性肝病，但对其发病机制的认识仍然有限。本研究旨在探讨高脂肪饮食 (HFD) 诱导和番茄红素干预的肝脂肪变性中的关键 lncRNA 和 mRNAs 及病理过程。我们分析了基因表达综合数据库 (GEO) 中 GSE146627 数据集的基因谱，以鉴定差异表达的 lncRNA 和 mRNA，并基于加权基因共表达网络分析 (WGCNA) 构建共表达网络。我们利用基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 数据库进行功能富集分析。我们发现，绿松石、蓝色、棕色、黄色、绿色和黑色模块与 NAFLD 显著相关。功能富集分析表明，一些关键 lncRNA（Smarca2、Tacc1、Flywch1 和 Mef2c）可能参与了 NAFLD 中炎症和代谢途径（如 TNF 信号、代谢、mTOR 信号、MAPK 信号和 p53 信号通路）的调节。NAFLD 小鼠模型的建立证实了番茄红素供应可减轻 HFD 诱导的 NAFLD 肝脂肪变性。我们的分析表明，炎症和代谢途径可能在 NAFLD 的发病机制中起关键作用，关键 lncRNA 为 NAFLD 提供了新的生物标志物、治疗思路和靶点。此外，番茄红素可能是预防 HFD 诱导的肝脂肪变性的植物化学物质。
