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

Fu Chen,Yunze Li,Wenlong Zhou,Yong Wang,Zhiyuan Wu,Yong Zhou

doi:10.3389/fendo.2020.611213

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.

Highlights

In the past few decades, obesity and its comorbidities are becoming the leading causes of death around the world [1]
nonalcoholic fatty liver disease (NAFLD) consists of a spectrum of pathological states ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) [2]
The results demonstrated that cellular zinc ion homeostasis process (P-value= 5.97E-13) was the most significantly enriched biological process (BP), followed by cellular response to cadmium ion process (P-value= 7.84E-13), zinc ion homeostasis process (P-value= 1.02E-12), and so on

Summary

Introduction

In the past few decades, obesity and its comorbidities are becoming the leading causes of death around the world [1]. As the incidence of advanced liver diseases such as cirrhosis and hepatocarcinoma are significantly increased in NASH patients, NASH becomes the second common cause of liver transplantation for liver diseases and is still growing [2]. A study showed that all NAFLD parameters improved after bariatric surgery. This effect is more significant in patients undergoing RYGB surgery than patients who undergo adjustable gastric banding (AGB) surgery [7]. As 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. The mechanism underlying RYGB induced NASH improvement is still elusive

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Discussion

Conclusion