Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome |
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Authors: | Deushi Michiyo Nomura Mitsunori Kawakami Akio Haraguchi Mihoko Ito Mizuho Okazaki Mitsuyo Ishii Hideto Yoshida Masayuki |
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Institution: | Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan. |
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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. |
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Keywords: | Metabolic syndrome Lipid metabolism Liver steatosis Insulin resistance NPC1L1 Ezetimibe |
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