A comprehensive bioinformatics analysis on multiple Gene Expression Omnibus datasets of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Abstract

Fatty liver disease is one of the leading causes of chronic damage in western countries. Approximately 25% of adults in the United States have fatty livers in the absence of excessive alcohol consumption, a condition termed nonalcoholic fatty liver disease (NAFLD). Little is known about the prevalence and genetic background of NAFLD or the factors that determine its development. In this study, we used the Gene-Cloud of Biotechnology Information bioinformatics platform to carry out a comprehensive bioinformatics analysis identifying differentially expressed genes (DEGs), key biological processes and intersecting pathways. We imported 3 Gene Expression Omnibus datasets (GSE31803, GSE49541, and GSE63067). Then, we assessed the expression of the DEGs in clinical samples. We found that CD24 was the only gene co-expressed in all 3 datasets. “Glycolysis/gluconeogenesis”, “p53 signaling pathway” and “glycine, serine and threonine metabolism” were 3 common pathways related to the fatty liver process. In NAFLD tissues, CD24, COL1A1, LUM, THBS2 and EPHA3 were upregulated, and PZP was downregulated. CD24 is a core gene among these DEGs and have not yet been studied of its impact on NAFLD. Co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in NAFLD progression. Further studies are needed to elucidate the mechanism of these potential genes and pathways in NAFLD.

Renalase Attenuates Mouse Fatty Liver Ischemia/Reperfusion Injury through Mitigating Oxidative Stress and Mitochondrial Damage via Activating SIRT1

“…A variety of chemicals, mainly drugs, and diets have been implicated in hepatic steatosis [68]. Moreover, recent studies have indicated that a number of genes play important roles in the development of NAFLD [69]. In the present study, we found that STAT3 was downregulated in NAFLD through bioinformatic analysis and further verified this result by RT-qPCR and western blotting.…”

Secondhand Smoke Induces Liver Steatosis through Deregulation of Genes Involved in Hepatic Lipid Metabolism

“…This network includes NF-κB, whose activation in non-parenchymal cells is generally recognized to promote inflammation, fibrosis and hepatocarcinogenesis [37]. Of significance is also the predicted activation of TP53, a preferential target of DNA-damaging agents, such as tobacco smoke carcinogens [30,50,51], and a key regulator in fatty liver and insulin resistance [52]. TP53 interacts with the NK-kB complex, and crosstalk between the TP53 and NF-kB transcription factors has been shown to play a pivotal role in determining the cellular response to certain stimuli, e.g., DNA damage [53].…”

Non‐alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion

“…Several studies in both experimental and clinical settings have shown the mRNA expression of the urea cycle enzymes and the physiological functional capacity to be parallel . This may also be the case in NAFLD where alteration in the hepatic transcriptome has been reported . However, such reports are mainly based on association studies providing limited insight into functional consequences of the altered gene expression and specifically, a possible gene regulatory basis for the deficient urea synthesis capacity has not been studied in NAFLD.…”

“…7 This may also be the case in NAFLD where alteration in the hepatic transcriptome has been reported. [8][9][10] However, such reports are mainly based on association studies providing limited insight into functional consequences of the altered gene expression and specifically, a possible gene regulatory basis for the deficient urea synthesis capacity has not been studied in NAFLD. The issue is important because compromised urea synthesis may lead to such clinical problems as hyperammonaemic cognitive dysfunction, as is already described in NAFLD 11 and favour the progression of disease.…”