Differentially expressed genes in mouse liver during development of fatty liver disease (FLD)

2004 ◽  
Vol 42 (08) ◽  
Author(s):  
M Villagrasa ◽  
DM Klass ◽  
KH Holzmann ◽  
G Adler ◽  
M Fuchs
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Differentially Expressed Genes ◽  
Fatty Liver Disease ◽  
Mouse Liver ◽  
Differentially Expressed

scholarly journals Combined Analysis of Expression Profiles in a Mouse Model and Patients Identified BHMT2 as a New Regulator of Lipid Metabolism in Metabolic-Associated Fatty Liver Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Yongqiang Ma ◽  
Zhi Tan ◽  
Qiang Li ◽  
Wenling Fan ◽  
Guangshun Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Differentially Expressed Genes ◽  
Fatty Liver Disease ◽  
Target Genes ◽  
Differentially Expressed ◽  
Overlapping Genes ◽  
Geo Database

Metabolic associated fatty liver disease (MAFLD) is associated with obesity, type 2 diabetes mellitus, and other metabolic syndromes. Farnesoid X receptor (FXR, NR1H4) plays a prominent role in hepatic lipid metabolism. This study combined the expression of liver genes in FXR knockout (KO) mice and MAFLD patients to identify new pathogenic pathways for MAFLD based on genome-wide transcriptional profiling. In addition, the roles of new target genes in the MAFLD pathogenic pathway were also explored. Two groups of differentially expressed genes were obtained from FXR-KO mice and MAFLD patients by transcriptional analysis of liver tissue samples. The similarities and differences between the two groups of differentially expressed genes were analyzed to identify novel pathogenic pathways and target genes. After the integration analysis of differentially expressed genes, we identified 134 overlapping genes, many of which have been reported to play an important role in lipid metabolism. Our unique analysis method of comparing differential gene expression between FXR-KO mice and patients with MAFLD is useful to identify target genes and pathways that may be strongly implicated in the pathogenesis of MAFLD. The overlapping genes with high specificity were screened using the Gene Expression Omnibus (GEO) database. Through comparison and analysis with the GEO database, we determined that BHMT2 and PKLR could be highly correlated with MAFLD. Clinical data analysis and RNA interference testing in vitro confirmed that BHMT2 may a new regulator of lipid metabolism in MAFLD pathogenesis. These results may provide new ideas for understanding the pathogenesis of MAFLD and thus provide new targets for the treatment of MAFLD.

scholarly journals Bioinformatics Analysis of Key Differentially Expressed Genes in Nonalcoholic Fatty Liver Disease Mice Models

2019 ◽  
Vol 19 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Chao Hou ◽  
Wenwen Feng ◽  
Shan Wei ◽  
Yulin Wang ◽  
Xiaoyi Xu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Differentially Expressed Genes ◽  
Fatty Liver Disease ◽  
Bioinformatics Analysis ◽  
Interaction Networks ◽  
Differentially Expressed ◽  
Molecular Characteristics ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a global health problem characterized by excessive accumulation of fat in the liver without effect of other pathological factors including hepatitis infection and alcohol abuse. Current studies indicate that gene factors play important roles in the development of NAFLD. However, the molecular characteristics of differentially expressed genes (DEGs) and associated mechanisms with NAFLD have not been well elucidated. Using two microarray data associated with the gene expression profiling in liver tissues of NAFLD mice models, we identified and selected several common key DEGs that contributed to NAFLD. Based on bioinformatics analysis, we discovered that the DEGs were associated with a variety of biological processes, cellular components, and molecular functions and were also related to several significant pathways. Via pathway crosstalk analysis based on overlapping DEGs, we observed that the identified pathways could form large and complex crosstalk networks. Besides, large and complex protein interaction networks of DEGs were further constructed. In addition, many hub host factors with a high degree of connectivity were identified based on interaction networks. Furthermore, significant modules in interaction networks were found, and the DEGs in the identified modules were found to be enriched with distinct pathways. Taken together, these results suggest that the key DEGs, associated pathways, and modules contribute to the development of NAFLD and might be used as novel molecular targets for the treatment of NAFLD.

scholarly journals Fish Oil Feeding Modulates the Expression of Hepatic MicroRNAs in a Western-Style Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Hualin Wang ◽  
Yang Shao ◽  
Fahu Yuan ◽  
Han Feng ◽  
Na Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fish Oil ◽  
Nonalcoholic Fatty Liver Disease ◽  
Rat Model ◽  
Fatty Liver Disease ◽  
Differentially Expressed ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Fish Oil Supplementation

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide. Recent studies have indicated that fish oil supplementation has benefits against NAFLD. Our previous transcriptomic study has validated the effect of fish oil supplementation on altering hepatic gene expression in a NAFLD rat model. In the current study, we examined the effects of fish oil on the expression of hepatic microRNAs. Male Sprague–Dawley rats were fed with a lab chow (CON), high-fat high-cholesterol diet (WD), or WD supplemented with fish oil (FOH), respectively. Small RNAs were extracted from livers for RNA-sequencing. A total of 79 miRNAs were identified as differentially expressed miRNAs (DEMs) between FOH and WD groups, exemplified by rno-miR-29c-3p, rno-miR-30d-5p, rno-miR-33-5p, rno-miR-34a, and rno-miR-328a-3p. Functional annotation of DEMs predicted target genes suggested that the altered hepatic miRNAs contributed to fish oil modification of hepatic lipid metabolism and signaling transduction. Integrative analysis of DEMs and differentially expressed genes suggested that the expression difference of Pcsk9, Insig2, Per3, and Socs1/3 between FOH and WD groups may be due to miRNA modification. Our study reveals that fish oil supplementation alters hepatic expression of miRNAs, which may contribute to fish oil amelioration of NAFLD in rats.

scholarly journals Tandem Mass Tag-based quantitative proteomics analysis of metabolic associated fatty liver disease induced by high fat diet in mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Hu Li ◽  
Wei Huang ◽  
Mingjie Wang ◽  
Peizhan Chen ◽  
Li Chen ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Mouse Liver ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
High Fat ◽  
Tandem Mass Tag ◽  
Hub Proteins

Abstract Background Although metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, the exact molecular mechanism of MAFLD progression remains unknown. In the present study, Tandem Mass Tag-labeled quantitative proteomic technology was used to elucidate the protein expression patterns of liver tissues in the progression of MAFLD, providing new potential therapeutic targets of it. Methods Five 6-week-old male C57BL/6 mice were fed with high fat diet (HFD) for 22 weeks to establish the MAFLD mouse models. Five C57BL/6 mice of the same age were fed with normal diet (ND) and taken as controls. Mice serum were sampled for biochemical tests, and livers were isolated for histopathological examinations. Six mouse liver samples (three from each group) were performed for proteomic analysis. Differentially expressed proteins were defined using fold change of > 1.5 or < 0.67 and p value < 0.05 as thresholds. Bioinformatic analysis was used to identify the hub proteins. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), Gene Expression Omnibus dataset, western blotting and immunohistochemistry were used to validate the expression of identified hub proteins. Results After 22 weeks on HFD diet, all mice developed MAFLD demonstrated by histopathological examination. Mouse body weights, liver weights, serum alanine transaminase and aspartate transaminase levels were significantly higher in the HFD group than ND group. Proteomics technology identified 4915 proteins in the mouse livers, among which 71 proteins were differentially expressed. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that majority of the differentially expressed proteins were involved in the peroxisome and peroxisome proliferator-activated receptor signaling pathway, as well as biosynthesis of unsaturated fatty acids. Protein–protein interaction analysis showed that these differentially expressed proteins interacted with each other and formed a complex network. Ten hub proteins were identified and validated using RT-qPCR. Five of these proteins were validated in the Gene Expression Omnibus dataset. Finally, Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase protein was validated in mouse liver tissue samples using western blotting and immunohistochemistry. Conclusion Our data showed that lipid metabolism-related pathways are closely associated with the development of MAFLD. The identified hub proteins might be novel targets for treating MAFLD.

scholarly journals Gene Set Enrichment Analysis (GSEA) of Differentially Expressed Genes in Green Tea against Methionine-Choline Deficient Diet in High-Fat Patients in the Development of Non-Alcoholic Fatty Liver Disease (NAFLD)

2018 ◽  
Author(s):  
Sarbojoy Saha ◽  
Ishtiaque Ahammad ◽  
Shampa Barmon
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Green Tea ◽  
Fatty Liver Disease ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
High Fat ◽  
Deficient Diet ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The most common liver disorder nowadays is non-alcoholic fatty liver disease(NAFLD) and it is a progressive disease that rises in severity from steatosis to nonalcoholic steatohepatitis(NASH), fibrosis and cirrhosis to increase risk of developing hepatocellular carcinoma. It is a cause of great concern as there is an estimated seventy million Americans who are currently affected by NAFLD, and this is expected to only increase because of its association with obesity and diabetes and also a lack of therapies to keep its development and progression in check. In this particular study we performed a gene set enrichment analysis(GSEA) of differentially expressed genes in a green tea against methionine-choline deficient diet in high-fat patients in the development of non-alcoholic fatty liver disease(NAFLD). The downregulated genes were used to perform an enrichment analysis and in the ARCHS4 TFs Coexpression database the most significant gene was found to be KLF5_human_tf_ARCHS4_coexpression. In the ARCHS4 Kinases Coexpression pathway database STYK1_human_kinase_ARCHS4 Coexpression was found to be the most significant gene. And finally for the upregulated genes a similar enrichment analysis was performed and in the humancy database &gamma;-linolenate biosynthesis_Homo sapiens_PWY-6000 gene was discovered to be the most significant one. This study has used bioinformatics tools and the Enrichr software to perform a comparative analysis of differentially expressed gene sets for high-fat patients having a diet consisting of green tea against a methionine-choline deficient diet. Green tea is known to contain several antioxidants and polyphenols which provide protection against many liver diseases such as non-alcoholic fatty liver disease(NAFLD). The present study simply tries to build awareness of this to the general public and allow them to learn more about certain diets which have protective effects against liver diseases. Hopefully by implementing these in their daily lifestyles the public can gain some form of protection against these types of liver disorders.

Exosomal miRNAs Profile in Children’s Nonalcoholic Fatty Liver Disease and the Correlation with Transaminase and Uric Acid

2020 ◽  
Vol 76 (1) ◽  
pp. 44-53 ◽  
Author(s):  
Xuelian Zhou ◽  
Ke Huang ◽  
Junjun Jia ◽  
Yan Ni ◽  
Jinna Yuan ◽  
...  
Keyword(s):  
Uric Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Acid Metabolism ◽  
Differentially Expressed ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Exosomal Mirnas

Objective: The incidence of non-alcoholic fatty liver disease (NAFLD) in children increased rapidly. However, the pathogenesis of NAFLD, especially how non-alcoholic fatty liver progress to non-alcoholic steatohepatitis, is still unclear. This study aims to explore the exosomal miRNAs profiles and the underline pathogenesis of child NAFLD. Methods: Twenty NAFLD and 20 health control were enrolled in this study. Circulating exosomes were isolated, and RNA sequencing was performed in test set (3 NAFLD/3 Controls). The differentially expressed miRNAs (DEM) were further validated in validation set (17 NAFLD/17 Controls). Spearman correlation ­analysis was used to investigate the association between DEM and clinical parameters. Results: Eighty-two miRNAs were differentially expressed (absolute fold change >2 and p < 0.05) in the 2 groups, they were involved in fat acid metabolism, starch and sucrose metabolism, bile acid metabolism and inflammation. miRNA122-5p, miRNA34a-5p, ­miRNA155-5p and miRNA146b-3p were up-regulated in NAFLD group (p < 0.05) and positively correlated with body mass index (r, 0.41–0.59), alanine aminotransferase (r, 0.36–0.52), aspartate transaminase (r, 0.31–0.48) and uric acid (UA, r, 0.51–0.69; p < 0.05). Conclusions: Circulating exosomal miRNAs may be involved in the pathogenesis of NAFLD and correlated with transaminase and UA.

Mouse Liver Dispersion for the Diagnosis of Early-Stage Fatty Liver Disease: A 70-Sample Study

2014 ◽  
Vol 40 (4) ◽  
pp. 704-713 ◽  
Author(s):  
Christopher T. Barry ◽  
Zaegyoo Hah ◽  
Alexander Partin ◽  
Robert A. Mooney ◽  
Kuang-Hsiang Chuang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Mouse Liver ◽  
Early Stage

scholarly journals Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

2018 ◽  
Vol 45 (4) ◽  
pp. 1487-1505 ◽  
Author(s):  
Jun Guo ◽  
Yuan Zhou ◽  
Yafen Cheng ◽  
Weiwei Fang ◽  
Gang Hu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transcriptome Profiling ◽  
Differentially Expressed ◽  
Disease Genes ◽  
Metformin Treatment ◽  
Alcoholic Fatty Liver ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

Background/Aims: Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. Methods: The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. Results: A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. Conclusions: The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD.

Sign in / Sign up

Export Citation Format

Share Document