Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome

被引：150

作者：

Deushi, Michiyo ^{[1
]}

Nomura, Mitsunori ^{[1
]}

Kawakami, Akio ^{[2
]}

Haraguchi, Mihoko ^{[1
]}

Ito, Mizuho ^{[4
]}

Okazaki, Mitsuyo ^{[3
]}

Ishii, Hideto ^{[1
]}

Yoshida, Masayuki ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Life Sci & Bioeth Res Ctr, Bunkyo Ku, Tokyo 1138510, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med, Dept Geriatr & Vasc Med, Tokyo 1138510, Japan

[3] Tokyo Med & Dent Univ, Coll Liberal Arts & Sci, Chem Lab, Chiba, Japan

[4] Skylight Biotech Inc, Tokyo, Japan

来源：

FEBS LETTERS | 2007年 / 581卷 / 29期

关键词：

metabolic syndrome; lipid metabolism; liver steatosis; insulin resistance; NPC1L1; ezetimibe;

D O I：

10.1016/j.febslet.2007.11.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：5664 / 5670

页数：7

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