TRIB3 Is a Hub Gene in Steatohepatitis and Aggravates Lipid Deposition and Inflammation in Hepatocytes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), also known as Metabolic dysfunction-associated fatty liver disease (MASLD), has become one of the most common chronic liver diseases worldwide, approximately 30% of adults and 70%~80% of patients with obesity and diabetes suffer from NAFLD. OBJECTIVE: We attempted to find a potential hub gene in NAFLD hepatocyte cell model induced by palmitic acid and oil acid (PAOA), and investigated the function of the hub-gene. METHODS: We searched and downloaded the GSE122660 dataset from GEO-DataSets, and differentially expressed genes (DEGs) were analyzed using R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to identify the significantly activated signaling pathways in steatohepatitis. A protein-protein interaction (PPI) network was constructed to identify hub genes among the DEGs. qRT-PCR, Western blotting, and Oil Red O staining were used to explore the function of hub genes in PAOA-induced hepatocytes in vitro. RESULTS: A total of 255 DEGs were identified in the GSE122660 dataset and were primarily associated with inflammation-and lipid metabolism-related pathways. The tribbles pseudokinase 3 (TRIB3) was highlighted as a hub gene. We found that TRIB3 was upregulated in CDHFDinduced NAFLD mouse liver tissue and hepatocyte cell models. Furthermore, TRIB3 aggravated PAOA-induced lipid accumulation and inflammation in hepatocytes in vitro. CONCLUSION: The present study identified TRIB3 as a hub gene for steatohepatitis and aggravated lipid accumulation and inflammation in vitro. Therefore, targeting TRIB3 could be a potential pharmacological strategy for NAFLD treatment.