Integrated Analysis of Key Genes and Pathways Involved in Nonalcoholic Steatohepatitis Improvement After Roux-en-Y Gastric Bypass Surgery

Abstract

BackgroundAs the incidence of nonalcoholic fatty liver disease (NAFLD) increases globally, nonalcoholic steatohepatitis (NASH) has become the second common cause of liver transplantation for liver diseases. Recent evidence shows that Roux-en-Y gastric bypass (RYGB) surgery obviously alleviates NASH. However, the mechanism underlying RYGB induced NASH improvement is still elusive.MethodsWe obtained datasets, including hepatic gene expression data and histologic NASH status, at baseline and 1 year after RYGB surgery. Differentially expressed genes (DEGs) were identified comparing gene expression before and after RYGB surgery in each dataset. Common DEGs were obtained between both datasets and further subjected to functional and pathway enrichment analysis. Protein–protein interaction (PPI) network was constructed, and key modules and hub genes were also identified.ResultsIn the present study, GSE106737 and GSE83452 datasets were included. One hundred thirty common DEGs (29 up-regulated and 101 down-regulated) were identified between GSE106737 and GSE83452 datasets. KEGG analysis showed that mineral absorption, IL-17 signaling pathway, osteoclast differentiation, and TNF signaling pathway were significantly enriched. Based on the PPI network, IGF1, JUN, FOS, LDLR, TYROBP, DUSP1, CXCR4, ATF3, CXCL2, EGR1, SAA1, CTSS, and PPARA were identified as hub genes, and three functional modules were also extracted.ConclusionThis study identifies the global gene expression change in the liver of NASH patients before and after RYGB surgery in a bioinformatic method. Our findings will contribute to the understanding of molecular biological changes underlying NASH improvement after RYGB surgery.

A novel immune-related genes signature after bariatric surgery is histologically associated with non-alcoholic fatty liver disease

“…Inhibition of TLRs could reduce the activation of MAPKs and NF-κB and ameliorate obesity-induced NAFLD [ 42 ]. CXCR4 was a G protein-coupled chemokine receptor and plays a key role in improving NAFLD after BS [ 43 ]. By increasing the affinity of CXCR4, CD4 + T-cells deposition were increased in the livers of NAFLD patients [ 44 ].…”

“…BS can manipulate adipocyte-derived adipocytokines (adiponectin, leptin, IL-6, etc.) to regulate NAFLD [ 43 ]. For example, BS could inhibit the activation of Kupffer cells and hepatic stellate cells (HSC) and reduces the expression of inflammatory genes by increasing adiponectin levels [ 48 ].…”

“…In addition, Johannie DP et al found that adipose tissue may directly promote the progression of NAFLD through inflammatory cytokines and immune cells, and they built a model using five genes to accurately predict the histological severity of NAFLD [ 20 ]. Fu C et al recently analysed the liver tissue after BS by bioinformatic method, and they found the potential key genes and pathways for Roux-en-Y gastric bypass to ameliorate NASH [ 43 ]. However, the liver tissue samples collected include hepatocytes and mesenchymal cells, which will affect the cellular composition of the liver tissue.…”

“…Neutrophils can recruit macrophages and dendritic cells to adipose tissue and play a major role in the initiation of inflammation [ 10 ]. Hypertrophy of adipocyte can secrete MCP-1/CCL2, promote the macrophages collect and produce proinflammatory cytokines TNFα, IL-6 and IL-10, resulting in NAFLD [ 43 ]. Dendritic cells in adipose tissue induce Th17 to secrete cytokines IL-6, IL-10 and IL-23, leading to more inflammation [ 50 ].…”

Dynamic co-expression modular network analysis in nonalcoholic fatty liver disease

“…Moreover, SAA1 was one of the 9 rewired nodes in health- and obesity-NAFL-NASH sequences. SAA1 acted as a hub gene of PPI network constructed by DEGs from NAFLD dataset GSE106737 and GSE83452 [ 18 ]. Increased hepatocyte SAA1 aggravated liver inflammation in NAFLD [ 19 ].…”