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.

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

“…HOMA‐IR, an essential indicator of systemic IR, is now elevated with HFD induction and relieved with LQ treatment. Previous studies have reported that the NAFLD model constructed by HFD is a high‐fat‐feeding obesity model, but the model is widely used in NAFLD research (Lahbib et al, 2015; Sui et al, 2023; Yan et al, 2022). With our current results, we found that LQ affected not only lipid metabolism but also glucose metabolism, so this suggests that the improvement of fatty liver by LQ may be accomplished through glucolipid metabolism.…”

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

“…Liu and colleagues additionally discovered that lncSNHG6 activates the interaction between mTOR and fas-associated factor family member 2 at ER-lysosome contacts and enhances the recruitment of mTORC1 to lysosomes in a cholesterol-dependent manner, further promoting the transition from MASLD to HCC [ 125 ]. Additionally, some lncRNA (Tacc1, lnc027912, Mef2c) are also involved in the reprogramming of lipid metabolism, such as mTOR/AMPK/SREBP 1c regulation in MASLD [ 174 , 175 ]. In addition, ncRNA can regulate the expression of FA transporter-related proteins.…”

Recent Insights into the Biomarkers, Molecular Targets and Mechanisms of Non-Alcoholic Steatohepatitis-Driven Hepatocarcinogenesis

“…Liu et al have further identified the long ncRNA (lncRNA) SNHG6 as an enhancer of cholesterol-dependent mTORC1 lysosomal recruitment and activator of FAF2-mTOR interaction at ER-lysosome contacts, which increased progression from NAFLD to HCC [ 148 ]. In addition, other long lncRNAs (lnc027912, Smarca2, Tacc1, Flywch1, and Mef2c) are involved in the regulation of the lipid accumulation, and inflammatory and metabolic pathways, such as mTOR/AMPK/SREBP1c signaling in NAFLD [ 149 , 150 ]. In addition to these results, Xu et al recently demonstrated by applying the bioinformatic analysis that PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy is inhibited in NASH mouse liver with fibrosis via the axis of upstream circular RNA 608 (circ608)-microRNA 222 (miR222)-PINK1 (circ608 inhibiting miR222) through mTOR and Wnt pathways [ 151 ].…”