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 sho © 2012 Pasarín et al.

Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD / M. Pasarín, V. La Mura, J. Gracia-Sancho, H. García-Calderó, A. Rodríguez-Vilarrupla, J.C. García-Pagán, J. Bosch, J.G. Abraldes. - In: PLOS ONE. - ISSN 1932-6203. - 7:4(2012 Apr 03), pp. e32785.1-e32785.9. [10.1371/journal.pone.0032785]

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

V. La Mura
Secondo
;
2012

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 sho © 2012 Pasarín et al.
fatty liver-disease; stellate cell activation; CCL4 cirrhotic rats; nitric-oxide; insulin-resistance; metabolic syndrome; in-vivo; nonalcoholic stetohepatitis; portal-hypertension; diabetes-mellitus
Settore MED/09 - Medicina Interna
Settore MED/12 - Gastroenterologia
3-apr-2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/288619
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