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.

scholarly journals Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis

Gut ◽  
2014 ◽  
Vol 64 (5) ◽  
pp. 800-812 ◽  
Author(s):  
Carlos J Pirola ◽  
Tomas Fernández Gianotti ◽  
Gustavo O Castaño ◽  
Pablo Mallardi ◽  
Julio San Martino ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Histology ◽  
Circulating Microrna ◽  
Disease Pathogenesis ◽  
Alcoholic Fatty Liver ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

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 γ-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.

scholarly journals Long Non-Coding RNAs Involved in Progression of Non-Alcoholic Fatty Liver Disease to Steatohepatitis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1883
Author(s):  
Biljana Atanasovska ◽  
Sander S. Rensen ◽  
Glenn Marsman ◽  
Ronit Shiri-Sverdlov ◽  
Sebo Withoff ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Human Liver ◽  
Target Genes ◽  
Alcoholic Fatty Liver ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is characterized by different stages varying from benign fat accumulation to non-alcoholic steatohepatitis (NASH) that may progress to cirrhosis and liver cancer. In recent years, a regulatory role of long non-coding RNAs (lncRNAs) in NAFLD has emerged. Therefore, we aimed to characterize the still poorly understood lncRNA contribution to disease progression. Transcriptome analysis in 60 human liver samples with various degrees of NAFLD/NASH was combined with a functional genomics experiment in an in vitro model where we exposed HepG2 cells to free fatty acids (FFA) to induce steatosis, then stimulated them with tumor necrosis factor alpha (TNFα) to mimic inflammation. Bioinformatics analyses provided a functional prediction of novel lncRNAs. We further functionally characterized the involvement of one novel lncRNA in the nuclear-factor-kappa B (NF-κB) signaling pathway by its silencing in Hepatoma G2 (HepG2) cells. We identified 730 protein-coding genes and 18 lncRNAs that responded to FFA/TNFα and associated with human NASH phenotypes with consistent effect direction, with most being linked to inflammation. One novel intergenic lncRNA, designated lncTNF, was 20-fold up-regulated upon TNFα stimulation in HepG2 cells and positively correlated with lobular inflammation in human liver samples. Silencing lncTNF in HepG2 cells reduced NF-κB activity and suppressed expression of the NF-κB target genes A20 and NFKBIA. The lncTNF we identified in the NF-κB signaling pathway may represent a novel target for controlling liver inflammation.

scholarly journals A comprehensive review of long non-coding RNAs in the pathogenesis and development of non-alcoholic fatty liver disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Arezoo Gowhari Shabgah ◽  
Fatemeh Norouzi ◽  
Mahdiyeh Hedayati-Moghadam ◽  
Davood Soleimani ◽  
Naseh Pahlavani ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Lipoprotein Metabolism ◽  
Alcoholic Fatty Liver ◽  
Fatty Acids Metabolism ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

AbstractOne of the most prevalent diseases worldwide without a fully-known mechanism is non-alcoholic fatty liver disease (NAFLD). Recently, long non-coding RNAs (lncRNAs) have emerged as significant regulatory molecules. These RNAs have been claimed by bioinformatic research that is involved in biologic processes, including cell cycle, transcription factor regulation, fatty acids metabolism, and-so-forth. There is a body of evidence that lncRNAs have a pivotal role in triglyceride, cholesterol, and lipoprotein metabolism. Moreover, lncRNAs by up- or down-regulation of the downstream molecules in fatty acid metabolism may determine the fatty acid deposition in the liver. Therefore, lncRNAs have attracted considerable interest in NAFLD pathology and research. In this review, we provide all of the lncRNAs and their possible mechanisms which have been introduced up to now. It is hoped that this study would provide deep insight into the role of lncRNAs in NAFLD to recognize the better molecular targets for therapy.

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