Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome
Open Access
- 20 November 2007
- journal article
- Published by Wiley in FEBS Letters
- Vol. 581 (29), 5664-5670
- https://doi.org/10.1016/j.febslet.2007.11.023
Abstract
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.Keywords
This publication has 35 references indexed in Scilit:
- Deficiency of Niemann-Pick C1 Like 1 Prevents Atherosclerosis in ApoE −/− MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2007
- Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family membersJCI Insight, 2007
- NPC1L1: Evolution From Pharmacological Target to Physiological Sterol TransporterArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Effect of Ezetimibe on Insulin Sensitivity and Lipid Profile in Obese and Dyslipidaemic PatientsCardiovascular Drugs and Therapy, 2006
- Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorptionJournal of Lipid Research, 2005
- Pitavastatin Inhibits Remnant Lipoprotein-Induced Macrophage Foam Cell Formation Through ApoB48 Receptor–Dependent MechanismArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Niemann-Pick C1 Like 1 Protein Is Critical for Intestinal Cholesterol AbsorptionScience, 2004
- Ezetimibe potently inhibits cholesterol absorption but does not affect acute hepatic or intestinal cholesterol synthesis in ratsBritish Journal of Pharmacology, 2003
- Steatohepatitis: A tale of two “hits”?Gastroenterology, 1998
- Absorption and Metabolism of Dietary CholesterolAnnual Review of Nutrition, 1983