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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/43658
Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD
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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.
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PASARÍN CASTELLANOS, Marcos, et al. Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD. PLoS One. 2012. Vol. 7, num. 2, pags. e32785. ISSN 1932-6203. [consulted: 8 of October of 2026]. Available at: https://hdl.handle.net/2445/43658