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. 2023 Feb 14;15(4):948.
doi: 10.3390/nu15040948.

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

Jing Sui  1   2 , Da Pan  2 , Junhui Yu  2 , Ying Wang  2 , Guiju Sun  2 , Hui Xia  2
Affiliations

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

Jing Sui et al. Nutrients. .

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.

Keywords: lncRNA; lycopene; nonalcoholic fatty liver disease; weighted gene coexpression network analysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The main workflow of the study. WGCNA, weighted correlation network analysis.
Figure 2
Figure 2
WGCNA was used to identify trait-related modules and genes. (a) Scale independence and mean connectivity analysis for various soft threshold powers. (b) Clustering dendrograms of lncRNAs and mRNAs. The color bands provide a simple visual comparison of module assignments based on the dynamic tree cutting method. WGCNA, weighted correlation network analysis.
Figure 3
Figure 3
Module–trait relationship. Each row represents a module eigengene and each column represents a trait. Each cell includes the corresponding correlation and p-value. HFD, high-fat diet; HFD-LYC, high-fat diet + lycopene.
Figure 4
Figure 4
Functional enrichment analysis for the turquoise and blue modules. Enriched GO analysis of mRNAs in the (a) turquoise and (b) blue modules; enriched KEGG pathway analysis of mRNAs in the (c) turquoise module and (d) blue modules.
Figure 4
Figure 4
Functional enrichment analysis for the turquoise and blue modules. Enriched GO analysis of mRNAs in the (a) turquoise and (b) blue modules; enriched KEGG pathway analysis of mRNAs in the (c) turquoise module and (d) blue modules.
Figure 5
Figure 5
Module lncRNA–mRNA network of hub genes in the turquoise (a) and blue (b) modules. Module lncRNA–mRNA pathway network of hub genes in the turquoise (c) and blue (d) modules. Red circles represent mRNAs, red and yellow triangles represent lncRNAs, and gray polygons represent pathways. The size of the circle represents the regulation capacity of the mRNA, where larger circles indicate relatively stronger regulation capacity.
Figure 5
Figure 5
Module lncRNA–mRNA network of hub genes in the turquoise (a) and blue (b) modules. Module lncRNA–mRNA pathway network of hub genes in the turquoise (c) and blue (d) modules. Red circles represent mRNAs, red and yellow triangles represent lncRNAs, and gray polygons represent pathways. The size of the circle represents the regulation capacity of the mRNA, where larger circles indicate relatively stronger regulation capacity.
Figure 5
Figure 5
Module lncRNA–mRNA network of hub genes in the turquoise (a) and blue (b) modules. Module lncRNA–mRNA pathway network of hub genes in the turquoise (c) and blue (d) modules. Red circles represent mRNAs, red and yellow triangles represent lncRNAs, and gray polygons represent pathways. The size of the circle represents the regulation capacity of the mRNA, where larger circles indicate relatively stronger regulation capacity.
Figure 6
Figure 6
Construction of protein–protein interaction (PPI) networks in the turquoise (a) and blue (b) modules. Red circles represent mRNA; the size of the circle represents the regulation capacity of mRNA, where larger circles indicate relatively stronger regulation capacity.
Figure 7
Figure 7
HE staining of the liver sections: (a) control group; (b) high-fat diet group; (c) high-fat diet + lycopene group. Magnification 200×.
Figure 7
Figure 7
HE staining of the liver sections: (a) control group; (b) high-fat diet group; (c) high-fat diet + lycopene group. Magnification 200×.
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