title: Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor.
  
  
  METHODS
  C57BL/6J mice were divided into five treatment groups as follows: basal diet (BD), high-fat diet (HFD) only, HFD with EZ (5mg/kg/day), HFD with AC (100mg/kg/day), and HFD with both EZ and AC for 24 weeks.
  
  
  RESULTS
  Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-alpha1 (PPAR-alpha1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model.
  
  
  CONCLUSIONS
  Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD.
authors: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors: Yuichi
authors: Y
authors: Nozaki
authors: Koji
authors: K
authors: Fujita
authors: Masato
authors: M
authors: Yoneda
authors: Koichiro
authors: K
authors: Wada
authors: Yoshiyasu
authors: Y
authors: Shinohara
authors: Hirokazu
authors: H
authors: Takahashi
authors: Hiroyuki
authors: H
authors: Kirikoshi
authors: Masahiko
authors: M
authors: Inamori
authors: Kensuke
authors: K
authors: Kubota
authors: Satoru
authors: S
authors: Saito
authors: Tetsuya
authors: T
authors: Mizoue
authors: Naohiko
authors: N
authors: Masaki
authors: Yoji
authors: Y
authors: Nagashima
authors: Yasuo
authors: Y
authors: Terauchi
authors: Atsushi
authors: A
authors: Nakajima
mesh_terms: D020909:Acarbose / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000069438:Ezetimibe; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D002352:Carrier Proteins; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D047493:PPAR alpha; D011973:Receptors, LDL; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D002784:Cholesterol; D000069438:Ezetimibe; D020909:Acarbose