Gut inflammation exacerbates hepatic injury in the high-fat diet induced NAFLD mouse: Attention to the gut-vascular barrier dysfunction.
Life Sci
; 209: 157-166, 2018 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-30096384
ABSTRACT
AIMS:
Gut inflammation has been put forward to be associated with hepatic injury in the clinical practice. The dismantled intestinal barrier was highly concerned, however, largely unknown about the role of gut-vascular barrier (GVB) in this process. This study aimed to investigate if inflamed gut directly contributes to the progression of non-alcoholic steatohepatitis (NASH), especially attention to the GVB dysfunction. MAINMETHODS:
Male C57bl/6 mice were fed with a high-fat diet (HFD) and 1% DSS for 12â¯weeks. The colonic inflammatory injury as well as hepatic injury were evaluated. The GVB function was assessed via measuring the permeability to fluorescently-labeled dextran (70â¯kDa) and the expression of plasmalemma vesicle-associated protein-1 (PV1). Furthermore, the plasma endotoxin level and hepatic TLR4/TLR9 mRNA expression were detected. KEYFINDINGS:
There were evident colitis in DSS-exposed mice, which trend to be more apparent in HFD ones. The HFDâ¯+â¯DSS mice exhibited more serious hepatic steatosis, inflammation and fibrosis than HFD groups. The downregulated tight junction protein in HFDâ¯+â¯DSS mice indicated loss of epithelial barrier. The GVB disruption were also confirmed with increased permeability to macromolecules and high expression of endothelial PV1 in HFDâ¯+â¯DSS mice. Accordingly, potentially elevated plasma endotoxin levels and markedly increased TLR4/TLR9 mRNA expression were demonstrated in HFDâ¯+â¯DSS mice rather than HFD groups.SIGNIFICANCE:
Gut inflammation exacerbates liver injury and fibrosis in HFD mice, which may contribute to the development of NASH. Beyond the damaged intestinal epithelial barrier, GVB disruption with bacterial translocation into may play a key role in the pathogenesis of NASH.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Vasculares
/
Trato Gastrointestinal
/
Modelos Animais de Doenças
/
Dieta Hiperlipídica
/
Hepatopatia Gordurosa não Alcoólica
/
Inflamação
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China