Combined with multiplex and network analysis to reveal the key genes and mechanisms of nonalcoholic fatty liver disease

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of chronic liver disease in developed countries, as a result of the worldwide trend of obesity and associated metabolic syndrome. Obesity and high-fat diet (HFD) are very common in patients with NAFLD. However, how to screen out key differentially expressed genes (DEGs) is a challenging task. The purpose of this study is to study the screen of key genes and pathways of HFD on the formation process of non-alcoholic fatty liver through network pharmacological analysis.

Methods: In this study, 173 genes associated with NAFLD were collected from the Gene Expression Omnibus (GEO) database. To find significant genes and pathways, combine network clustering analysis, topology analysis, and pathway analysis.

Results: The results showed that there were four key signaling pathways related to HFD, including complement cascade, Atorvastatin ADME, Asthma and Aflatoxin activation and detoxification. In addition, we identified six representative key genes, including Ccl5, Tlr2, Cd274, Cxcl10, Cxcl9 and Cd74, and screened three intersecting genes in Mus musculus and Homo sapiens sample, including C3, F2 and C7.

Conclusions: In conclusion, our study constructed the NAFLD gene regulatory network of C57BL/6J mice for the first time and jointly analyzed the Mus musculus samples and Homo sapiens samples. It provides new insights for identifying potential biomarkers and valuable therapeutic clues, and puts forward a new method for web-based research. These findings may provide potential targets for early diagnosis, effective therapy and prognostic markers of NAFLD.

Keywords: Diet-induced obesity mouse; Gene; High-fat diet; Network; Pathway.