Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes
Experimental & Molecular Medicine
; : e283-2017.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-85455
Biblioteca responsável:
WPRO
ABSTRACT
We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, P<0.05). Gene-metabolite network analysis identified ccl2 and jun as hubs with the largest connections to other genes, which were mainly involved in tumor necrosis factor, P53, nuclear factor-kappa B, chemokine, peroxisome proliferator activated receptor and Toll-like receptor signaling pathways. The specifically regulated genes and metabolites in different NAFLD phenotypes constructed their own networks, which were mainly involved in the lipid and fatty acid metabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fenótipo
/
Proteínas do Sistema Complemento
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Fator de Necrose Tumoral alfa
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Estreptozocina
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Peroxissomos
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Modelos Animais
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Diabetes Mellitus
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Dieta
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Receptores Toll-Like
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Proteínas Quinases Ativadas por AMP
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2017
Tipo de documento:
Artigo