Integrated Bioinformatics Analysis Reveals Potential Mechanisms Associated with Intestinal Flora Intervention in Non-alcoholic Fatty Liver Disease

Author(s):  
Yingying Liu ◽  
Xinkui Liu ◽  
Wei Zhou ◽  
Jingyuan Zhang ◽  
Siyu Guo ◽  
...  

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease that imposes a huge economic burden on global public health. And the gut-liver axis theory supports the therapeutic role of intestinal flora in the development and progression of NAFLD. To this end, we designed bioinformatics study on the relationship between intestinal flora disorder and NAFLD, so as to explore the molecular mechanism of intestinal flora interfering with NAFLD. Methods Differentially expressed genes for NAFLD were obtained from GEO database. And the disease genes for NAFLD and intestinal flora disorder were obtained from the disease databases. Using string 11.0 database to establish protein-protein interaction network relationship and cytoscape 3.7.2 software visualization. Cytoscape plug-in MCODE and cytoHubba were used to screen the potential genes of intestinal flora disorder and NAFLD, so as to obtain potential targets for intestinal flora to interfere in the occurrence and process of NAFLD. Enrichment analysis of potential targets was carried out using R 4.0.2 software. Results The results showed that PTGS2, SPINK1 and C5AR1 may be the key genes for intestinal flora to interfere with NAFLD. CCL2, IL6, IL1B and FOS may be key genes for the development and progression of NAFLD. The gene function is mainly reflected in basic biological processes, including the regulation of metabolic process, epithelial development and immune influence. The pathway is mainly related to signal transduction, immune regulation and physiological metabolism. The TNF signaling pathway, AGE-RAGE signaling pathway in the diabetic activity, and NF-Kappa B signaling pathways are important pathways for intestinal flora to interfere with NAFLD. Conclusion According to the analysis results, there is a certain correlation between intestinal flora disorder and NAFLD. It is speculated that the mechanism by which intestinal flora may interfere with the occurrence and development of NAFLD is mainly related to inflammatory response and insulin resistance. Nevertheless, further research is needed to explore the specific molecular mechanisms.

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  

2021 ◽  
Author(s):  
Pu Yifu

Abstract Purpose Many studies show correlation between polycystic ovary syndrome(PCOS) and non-alcoholic fatty liver disease(NAFLD),but the underlying pathogenic genes are not clear. This study by using the bioinformatics method aims to search the key genes involved in these 2 diseases. Methods The Gene Expression Omnibus (GEO) datasets coming from the GEO database GSE63067 -NAFLD patients and healthy controls, and GSE34526 -PCOS patients and normal controls, are downloaded. Differentially expressed genes (DEGs) of 2 diseases datasets and the common genes are obtained. After GO and KEGG enrichment analyses of common genes are performed. To find the key genes between NAFLD and PCOS, a protein–protein interaction (PPI) network is carried out. In addition, the diagnostic value of key genes in PCOS is analyzed. Results According to NAFLD and PCOS downloaded datasets,34 common genes,21 key genes,15 GO terms and 4 KEGG pathways are obtained. Further,based on the top 6 key genes,the corresponding area under the curve (AUC) by constructing ROC curves in the PCOS is 0.909 (95% CI, 0.775–1.000). Conclusions The study identify some key genes in the occurrence and progression between NAFLD and PCOS. In the future,to verify our results,it need experimental and clinical research.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1903
Author(s):  
Tae Hyun Kim ◽  
Dong-Gyun Hong ◽  
Yoon Mee Yang

The liver plays a key role in maintaining energy homeostasis by sensing and responding to changes in nutrient status under various metabolic conditions. Recently highlighted as a major endocrine organ, the contribution of the liver to systemic glucose and lipid metabolism is primarily attributed to signaling crosstalk between multiple organs via hepatic hormones, cytokines, and hepatokines. Hepatokines are hormone-like proteins secreted by hepatocytes, and a number of these have been associated with extra-hepatic metabolic regulation. Mounting evidence has revealed that the secretory profiles of hepatokines are significantly altered in non-alcoholic fatty liver disease (NAFLD), the most common hepatic manifestation, which frequently precedes other metabolic disorders, including insulin resistance and type 2 diabetes. Therefore, deciphering the mechanism of hepatokine-mediated inter-organ communication is essential for understanding the complex metabolic network between tissues, as well as for the identification of novel diagnostic and/or therapeutic targets in metabolic disease. In this review, we describe the hepatokine-driven inter-organ crosstalk in the context of liver pathophysiology, with a particular focus on NAFLD progression. Moreover, we summarize key hepatokines and their molecular mechanisms of metabolic control in non-hepatic tissues, discussing their potential as novel biomarkers and therapeutic targets in the treatment of metabolic diseases.


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