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PLoS One. 2012;7(4):e32785. doi: 10.1371/journal.pone.0032785. Epub 2012 Apr 3.

Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD.

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1
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, CIBERrehd, University of Barcelona, Barcelona, Spain.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation.

PMID:
22509248
PMCID:
PMC3317918
DOI:
10.1371/journal.pone.0032785
[Indexed for MEDLINE]
Free PMC Article
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