Identification and Evaluation of Hub Long Noncoding RNAs and mRNAs in High Fat Diet Induced Liver Steatosis

Abstract

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.