Systems-level organization of non-alcoholic fatty liver disease progression network,Molecular BioSystems

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Systems-level organization of non-alcoholic fatty liver disease progression network
Molecular BioSystems Pub Date : 2017-07-14 00:00:00 , DOI: 10.1039/c7mb00013h
K. Shubham _{1,

2,

3,

4} , L. Vinay _{1,

2,

3,

4} , P. K. Vinod _{1,

2,

3,

4}

Affiliation

Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex spectrum of diseases ranging from simple steatosis to Non-Alcoholic Steatohepatitis (NASH) with fibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is complex, involving crosstalk between multiple organs, cell-types, and environmental and genetic factors. Dysfunction of the adipose tissue plays a central role in NAFLD progression. Here, we analysed transcriptomics data obtained from the Visceral Adipose Tissue (VAT) of NAFLD patients to understand how the VAT metabolism is altered at the genome scale and co-regulated with other cellular processes during the progression from obesity to NASH with fibrosis. For this purpose, we performed Weighted Gene Co-expression Network Analysis (WGCNA), a method that organizes the disease transcriptome into functional modules of cellular processes and pathways. Our analysis revealed the coordination of metabolic and inflammatory modules (termed “immunometabolism”) in the VAT of NAFLD patients. We found that genes of arachidonic acid, sphingolipid and glycosphingolipid metabolism were upregulated and co-expressed with genes of proinflammatory signalling pathways and hypoxia in NASH/NASH with fibrosis. We hypothesize that these metabolic alterations might play a role in sustaining VAT inflammation. Furthermore, immunometabolism related genes were also co-expressed with genes involved in Extracellular Matrix (ECM) degradation. Our analysis indicates that upregulation of both ECM degrading enzymes and their inhibitors (incoherent feedforward loop) potentially leads to the ECM deposition in the VAT of NASH with fibrosis patients.

中文翻译：

非酒精性脂肪肝疾病进展网络的系统级组织

非酒精性脂肪性肝病（NAFLD）是一系列疾病，从单纯性脂肪变性到伴有纤维化的非酒精性脂肪性肝炎（NASH），可能发展为肝硬化和肝细胞癌。NAFLD的发病机制很复杂，涉及多个器官，细胞类型以及环境和遗传因素之间的串扰。脂肪组织的功能障碍在NAFLD进展中起重要作用。在这里，我们分析了从NAFLD患者的内脏脂肪组织（VAT）获得的转录组学数据，以了解VAT代谢如何在基因组规模上发生改变，并在从肥胖症发展为纤维化NASH的过程中与其他细胞过程共同调控。为此，我们进行了加权基因共表达网络分析（WGCNA），一种将疾病转录组组织成细胞过程和途径的功能模块的方法。我们的分析揭示了NAFLD患者增值税中代谢和炎症模块（称为“免疫代谢”）的协调。我们发现花生四烯酸，鞘脂和糖鞘脂代谢的基因在纤维化的NASH / NASH中与促炎性信号通路和缺氧的基因共表达并共表达。我们假设这些代谢改变可能在维持增值税炎症中起作用。此外，免疫代谢相关基因也与参与细胞外基质（ECM）降解的基因共表达。

更新日期：2017-07-28

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