Abstract

BackgroundA progressive development of hepatic steatosis with an increase in the lipid hepatocyte content and the formation of megamitochondria have been demonstrated in rats with prehepatic portal hypertension. The aim of this study is to verify the existence of liver and serum lipid metabolism impairments in rats with long-term (2 years) portal hypertension.MethodsMale Wistar rats: Control (n = 10) and with prehepatic portal hypertension by triple partial portal vein ligation (n = 9) were used. Liver content of Triglycerides (TG), phospholipids (PL) and cholesterol and serum cholesterol, lipoproteins (HDL and LDL), TG, glucose and Lipid Binding Protein (LBP) were assayed with specific colorimetric commercial kits. Serum levels of insulin and somatostatin were assayed by RIA.ResultsThe liver content of TG (6.30 ± 1.95 vs. 4.17 ± 0.59 μg/ml; p < 0.01) and cholesterol (1.48 ± 0.15 vs. 1.10 ± 0.13 μg/ml; p < 0.001) increased in rats with portal hypertension. The serum levels of cholesterol (97.00+26.02 vs. 114.78 ± 37.72 mg/dl), TG (153.41 ± 80.39 vs. 324.39 ± 134.9 mg/dl; p < 0.01), HDL (20.45 ± 5.14 vs. 55.15 ± 17.47 mg/dl; p < 0.001) and somatostatin (1.32 ± 0.31 vs. 1.59 +0.37 mg/dl) decreased, whereas LDL (37.83 ± 15.39 vs. 16.77 ± 6.81 mg/dl; p < 0.001) and LBP (308.47 ± 194.53 vs. 60.27 ± 42.96 ng/ml; p < 0.001) increased.ConclusionPortal hypertension in the rat presents changes in the lipid and carbohydrate metabolisms similar to those produced in chronic inflammatory conditions and sepsis in humans. These underlying alterations could be involved in the development of hepatic steatosis and, therefore, in those described in the metabolic syndrome in humans.

Highlights

  • A progressive development of hepatic steatosis with an increase in the lipid hepatocyte content and the formation of megamitochondria have been demonstrated in rats with prehepatic portal hypertension

  • These underlying alterations could be involved in the development of hepatic steatosis and, in those described in the metabolic syndrome in humans

  • Splanchnic changes related to portal hypertension The existence of portal hyperpressure in the long-term (22 months) in this experimental model of triple partial portal vein ligation was confirmed by the development of portal hyperpressure, mesenteric venous vasculopathy, splenomegaly and portal-systemic collateral circulation

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Summary

Introduction

A progressive development of hepatic steatosis with an increase in the lipid hepatocyte content and the formation of megamitochondria have been demonstrated in rats with prehepatic portal hypertension. Portal Hypertension (PH) is a clinical syndrome defined by a pathological increase in blood pressure in the portal system [1,2] It is one of the most frequent and serious complications of chronic liver disease [1,2]. Lipids in Health and Disease 2008, 7:4 http://www.lipidworld.com/content/7/1/4 complications are related to the obstruction to the portal flow [1,2] These alterations are splanchnic, like the development of portosystemic vessels, splenomegaly or portal hypertensive enteropathy, and extrasplanchnic, such as encephalopathy or hepato-pulmonary syndrome [2]. We have shown that prehepatic PH by triple partial portal vein ligation (TPVL) in the rat produces microvesicular hepatocytic fatty infiltration with megamitochondria and an impairment of the liver lipid metabolism in the short (1 month) and long-term (1 year) [6,7,8]. Liver steatosis was described in rats with PH [9] and this association was already suggested in humans over 30 years ago [10]

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