Journal
FEBS LETTERS
Volume 581, Issue 29, Pages 5664-5670Publisher
WILEY
DOI: 10.1016/j.febslet.2007.11.023
Keywords
metabolic syndrome; lipid metabolism; liver steatosis; insulin resistance; NPC1L1; ezetimibe
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Non-alcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome characterized by dislipidemia and insulin resistance. We hypothesized that ezetimibe, an inhibitor of NPC1L1, improves these metabolic disorders in Zucker obese fatty rats (ZOF). Ezetimibe significantly lowered total cholesterol and triglycerides in ZOF with prominent reduction in the remnant lipoprotein fraction and small dense low density lipoprotein fraction. Moreover, lipid deposition and fibrosis of liver were decreased by ezetimibe. Interestingly, ezetimibe improved insulin and plasma glucose response after intraperitoneal glucose injection. Further, ezetimibe enhanced insulin signaling in cultured hepatocytes. Our results indicate the potential of ezetimibe in treating the metabolic syndrome and NAFLD. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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