scholarly journals Potential Regulators Driving the Transition in Nonalcoholic Fatty Liver Disease: a Stage-Based View

2017 ◽  
Vol 41 (1) ◽  
pp. 239-251 ◽  
Author(s):  
Yi Lou ◽  
Yi-Dan Chen ◽  
Fu-Rong Sun ◽  
Jun-Ping Shi ◽  
Yu Song ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Regulatory Network ◽  
Fatty Liver Disease ◽  
Large Scale ◽  
Functional Organization ◽  
Transcriptional Regulators ◽  
Nonalcoholic Fatty Liver

Background and Aim: The incidence of nonalcoholic fatty liver disease (NAFLD), ranging from mild steatosis to hepatocellular injury and inflammation, increases with the rise of obesity. However, the implications of transcription factors network in progressive NAFLD remain to be determined. Methods: A co-regulatory network approach by combining gene expression and transcription influence was utilized to dissect transcriptional regulators in different NAFLD stages. In vivo, mice models of NAFLD were used to investigate whether dysregulated expression be undertaken by transcriptional regulators. Results: Through constructing a large-scale co-regulatory network, sample-specific regulator activity was estimated. The combinations of active regulators that drive the progression of NAFLD were identified. Next, top regulators in each stage of NAFLD were determined, and the results were validated using the different experiments and bariatric surgical samples. In particular, Adipocyte enhancer-binding protein 1 (AEBP1) showed increased transcription activity in nonalcoholic steatohepatitis (NASH). Further characterization of the AEBP1 related transcription program defined its co-regulators, targeted genes, and functional organization. The dynamics of AEBP1 and its potential targets were verified in an animal model of NAFLD. Conclusions: This study identifies putative functions for several transcription factors in the pathogenesis of NAFLD and may thus point to potential targets for therapeutic interventions.

scholarly journals The interplay of microRNAs and transcription factors in autophagy regulation in nonalcoholic fatty liver disease

2021 ◽  
Author(s):  
Yumi Kim ◽  
Da-Hye Lee ◽  
So-Hyun Park ◽  
Tae-Il Jeon ◽  
Chang Hwa Jung
Keyword(s):  
Transcription Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Posttranscriptional Regulation ◽  
Fatty Liver Disease ◽  
Regulatory Networks ◽  
Nonalcoholic Fatty Liver ◽  
Autophagy Pathway ◽  
Cytoplasmic Processes

AbstractThe autophagy-lysosomal degradation system has an important role in maintaining liver homeostasis by removing unnecessary intracellular components. Impaired autophagy has been linked to nonalcoholic fatty liver disease (NAFLD), which includes hepatitis, steatosis, fibrosis, and cirrhosis. Thus, gaining an understanding of the mechanisms that regulate autophagy and how autophagy contributes to the development and progression of NAFLD has become the focus of recent studies. Autophagy regulation has been thought to be primarily regulated by cytoplasmic processes; however, recent studies have shown that microRNAs (miRNAs) and transcription factors (TFs) also act as key regulators of autophagy by targeting autophagy-related genes. In this review, we summarize the miRNAs and TFs that regulate the autophagy pathway in NAFLD. We further focus on the transcriptional and posttranscriptional regulation of autophagy and discuss the complex regulatory networks involving these regulators in autophagy. Finally, we highlight the potential of targeting miRNAs and TFs involved in the regulation of autophagy for the treatment of NAFLD.

Identification of key target genes and pathway analysis in nonalcoholic fatty liver disease via integrated bioinformatics analysis

2020 ◽  
Author(s):  
Xi Chen ◽  
Lian Zhang ◽  
Yanyan Wang ◽  
Ruien Li ◽  
Ming Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Regulatory Network ◽  
Fatty Liver Disease ◽  
Target Genes ◽  
Point Group ◽  
Nonalcoholic Fatty Liver ◽  
Time Point

Abstract Background This study aimed to explore the mechanisms underlying nonalcoholic fatty liver disease (NAFLD) and develop new diagnostic biomarkers for nonalcoholic steatohepatitis (NASH). Methods The microarray dataset GES83452 was downloaded from the NCBI-GEO database, and the differentially expressed RNAs (DERs) were screened between the NAFLD and non-NAFLD samples of the baseline and 1-year follow-up time point group based on the Limma package. Subsequently, the lncRNA–miRNA–mRNA regulation network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the regulated target genes in the ceRNA regulatory network were performed based on DAVID. Finally, PharmGKB database was used to search for the gene-related drug molecules, and the gene–drug connection network was constructed. Results A total of 561 DERs (268 downregulated and 293 upregulated) were screened in the baseline time point group, and 1163 DERs (522 downregulated and 641 upregulated) were screened in the 1-year follow-up time point group. A total of 74 lncRNA–miRNA pairs and 523 miRNA–mRNA pairs were obtained to construct lncRNA–miRNA–mRNA regulatory network. Subsequently, functional enrichment analysis revealed 28 GO and 9 KEGG pathways in the ceRNA regulatory network. LEPR and CXCL10 are involved in the Cytokine–cytokine receptor interaction (P = 1.86E-02), and the FOXO1 is involved in both the Insulin signaling pathway (P = 1.79E-02) and the pathways in cancer (P = 2.87E-02). Conclusion LEPR, CXCL10, and FOXO1 were the characteristic target genes for NAFLD.

scholarly journals Body weight variability and the risk of cardiovascular outcomes in patients with nonalcoholic fatty liver disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mi Na Kim ◽  
Kyungdo Han ◽  
Juhwan Yoo ◽  
Yeonjung Ha ◽  
Young Eun Chon ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Large Scale ◽  
Health Examination ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk ◽  
All Cause Mortality

AbstractWe investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.56 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.

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