Ezetimibe improves liver steatosis and insulin resistance in obese rat model of metabolic syndrome.
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.
Deushi
Michiyo
M
Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
Nomura
Mitsunori
M
Kawakami
Akio
A
Haraguchi
Mihoko
M
Ito
Mizuho
M
Okazaki
Mitsuyo
M
Ishii
Hideto
H
Yoshida
Masayuki
M
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002478:Cells, Cultured; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000378:metabolism; D000069438:Ezetimibe; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000008:administration & dosage; D024821:Metabolic Syndrome / Q000188:drug therapy*; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D011924:Rats, Zucker; D013997:Time Factors
D000924:Anticholesteremic Agents; D001384:Azetidines; D001786:Blood Glucose; D008055:Lipids; D000069438:Ezetimibe