Syndrome differentiation of fatty liver based on the whole network analysis theory

2010 ◽  
Author(s):  
Shouyi Yin ◽  
Tao Liu ◽  
Huafeng Wei ◽  
Guang Ji
Keyword(s):  
Network Analysis ◽  
Fatty Liver ◽  
Syndrome Differentiation ◽  
Analysis Theory

scholarly journals A network-based approach reveals the dysregulated transcriptional regulation in non-alcohol fatty liver disease

2021 ◽  
Author(s):  
Hong Yang ◽  
Muhammad Arif ◽  
Meng Yuan ◽  
Xiangyu Li ◽  
Koeun Shong ◽  
...  
Keyword(s):  
Liver Disease ◽  
Network Analysis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cholesterol Metabolism ◽  
Metabolic Model ◽  
Biological Processes ◽  
Hepatic Expression ◽  
Expression Of Genes ◽  
Using Data

Non-alcohol-related fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. We performed network analysis to investigate the dysregulated biological processes in the disease progression and revealed the molecular mechanism underlying NAFLD. Based on network analysis, we identified a highly conserved disease-associated gene module across three different NAFLD cohorts and highlighted the predominant role of key transcriptional regulators associated with lipid and cholesterol metabolism. In addition, we revealed the detailed metabolic differences between heterogenous NAFLD patients through integrative systems analysis of transcriptomic data and liver-specific genome-scale metabolic model. Furthermore, we identified transcription factors (TFs), including SREBF2, HNF4A, SREBF1, YY1 and KLF13, showing regulation of hepatic expression of genes in the NAFLD-associated modules and validated the TFs using data generated from a mouse NAFLD model. In conclusion, our integrative analysis facilitated our understanding of the regulatory mechanism of these perturbed TFs and associated biological processes.

scholarly journals Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes

2017 ◽  
Vol 49 (1) ◽  
pp. e283-e283 ◽  
Author(s):  
Xiao-Lin Liu ◽  
Ya-Nan Ming ◽  
Jing-Yi Zhang ◽  
Xiao-Yu Chen ◽  
Min-De Zeng ◽  
...  
Keyword(s):  
Liver Disease ◽  
Network Analysis ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Disease Phenotypes ◽  
Metabolite Network

scholarly journals Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yo Han Lee ◽  
Hyun-Jun Jang ◽  
Sounkou Kim ◽  
Sun Sil Choi ◽  
Keon Woo Khim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Network Analysis ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Synergic Effect ◽  
Hepatic Lipid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid

Background:Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods:Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results:We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions:Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding:This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940), and the Future-leading Project Research Fund (1.210034.01) of UNIST.

scholarly journals Hepatic miR-20b promotes nonalcoholic fatty liver disease by suppressing PPARα

2021 ◽  
Author(s):  
Yo Han Lee ◽  
Hyun-Jun Jang ◽  
Sounkou Kim ◽  
Sun Sil Choi ◽  
Keon Woo Khim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Network Analysis ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Metabolic Reprogramming ◽  
Deficient Diet ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic metabolic reprogramming that leads to excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic metabolic reprogramming, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods: Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in NAFLD patients, we revealed that miR-20b specifically targets PPARα. miR-20b mimic and anti-miR-20b were administered to hepatocytes as well as high fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of miR-20b in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by miR-20b. Results: We revealed that miR-20b specifically targets PPARα through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of miR-20b was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of miR-20b significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, miR-20b significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARα. In miR-20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of miR-20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Conclusions: Taken together, our results demonstrate that the novel miR-20b targets PPARα, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding: This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340), the Future-leading Project Research Fund (1.210034.01) of UNIST and the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1I1A1A01074940).

scholarly journals Dynamic co-expression modular network analysis in nonalcoholic fatty liver disease

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Jing Zheng ◽  
Huizhong Wu ◽  
Zhiying Zhang ◽  
Songqiang Yao
Keyword(s):  
Liver Disease ◽  
Network Analysis ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Dynamic Networks ◽  
Gene Set Enrichment Analysis ◽  
Molecular Networks ◽  
Nonalcoholic Fatty Liver ◽  
Modular Analysis

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease affecting people’s health worldwide. Exploring the potential biomarkers and dynamic networks during NAFLD progression is urgently important. Material and methods Differentially expressed genes (DEGs) in obesity, NAFL and NASH were screened from GSE126848 and GSE130970, respectively. Gene set enrichment analysis of DEGs was conducted to reveal the Gene Ontology (GO) biological process in each period. Dynamic molecular networks were constructed by DyNet to illustrate the common and distinct progression of health- or obesity-derived NAFLD. The dynamic co-expression modular analysis was carried out by CEMiTool to elucidate the key modulators, networks, and enriched pathways during NAFLD. Results A total of 453 DEGs were filtered from obesity, NAFL and NASH periods. Function annotation showed that health-NAFLD sequence was mainly associated with dysfunction of metabolic syndrome pathways, while obesity-NAFLD sequence exhibited dysregulation of Cell cycle and Cellular senescence pathways. Nine nodes including COL3A1, CXCL9, CYCS, CXCL10, THY1, COL1A2, SAA1, CDKN1A, and JUN in the dynamic networks were commonly identified in health- and obesity-derived NAFLD. Moreover, CYCS, whose role is unknown in NAFLD, possessed the highest correlation with NAFLD activity score, lobular inflammation grade, and the cytological ballooning grade. Dynamic co-expression modular analysis showed that module 4 was activated in NAFL and NASH, while module 3 was inhibited at NAFLD stages. Module 3 was negatively correlated with CXCL10, and module 4 was positively correlated with COL1A2 and THY1. Conclusion Dynamic network analysis and dynamic gene co-expression modular analysis identified a nine-gene signature as the potential key regulator in NAFLD progression, which provided comprehensive regulatory mechanisms underlying NAFLD progression.

scholarly journals Antifibrotic Effects of Kangxian Ruangan Capsule on Rats with Nonalcoholic Fatty Liver Fibrosis and Hepatic Stellate Cells through Regulation of TGF-β and TLR4 Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Liming Liu ◽  
Ying Zhou ◽  
Dan Dai ◽  
Hongmei Xia ◽  
Kang Zhao ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Stellate Cells ◽  
Syndrome Differentiation ◽  
G1 Arrest ◽  
Tlr4 Signaling ◽  
Nonalcoholic Fatty Liver

Kangxian ruangan (KXRG) is a traditional Chinese medicine (TCM) formula consisting of 12 herbs. TCM syndrome differentiation proposes that KXRG exerts pharmacological effects against nonalcoholic fatty liver disease (NAFLD) fibrosis. This work investigates the effect of KXRG on NAFLD fibrosis in vivo and in vitro. In vivo, the NAFLD fibrosis model was constructed in Wistar rats using methionine- and choline-deficient (MCD) diet, followed by KXRG (0.92 g/kg/d) treatment for 8 weeks. In vitro, primary hepatic stellate cells (HSCs) were activated using platelet-derived growth factor (PDGF) and treated with KXRG. Molecular mechanisms underlying fibrosis were investigated. After 8 weeks, compared with the control groups, the histological lesions, degree of fibrosis, and inflammatory reaction increased with the MCD diet as demonstrated by histological changes and increased fibrosis-related (α-SMA, TGF-β, COL1A1, and desmin, P < 0.01 ) and inflammation-related factors (TNF-α, MCP-1, and F4/80, P < 0.01 ), whereas they decreased with KXRG treatment ( P < 0.01 ). KXRG not only inhibited the proliferation of activated HSCs and promoted their apoptosis but also resulted in G0-G1 arrest. Furthermore, KXRG suppressed HSC activation ( P < 0.01 ), collagen synthesis ( P < 0.01 ), and α-SMA expression ( P < 0.01 ) with PDGF stimulation. In both the MCD diet-induced animal model and PDGF-induced cell model, KXRG inhibited TGF-β and TLR4 signaling ( P < 0.01 ), similar to corresponding small-molecule inhibitors. These results demonstrated that KXRG might exert suppressive effects against NAFLD fibrosis via regulating TGF-β and TLR4 signaling. KXRG may act as a natural and potent therapeutic agent against NAFLD.

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