Long-term combination therapy of ezetimibe and acarbose for non-alcoholic fatty liver disease.

Abstract

BACKGROUND/AIMS:

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: Yuichi Nozaki, Koji Fujita, Masato Yoneda, Koichiro Wada, Yoshiyasu Shinohara, Hirokazu Takahashi, Hiroyuki Kirikoshi, Masahiko Inamori, Kensuke Kubota, Satoru Saito, Tetsuya Mizoue, Naohiko Masaki, Yoji Nagashima, Yasuo Terauchi, Atsushi Nakajima
• Journal: Journal of hepatology (J Hepatol) Vol. 51 Issue 3 Pg. 548-56 (Sep 2009) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 19596472 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Azetidines
• Carrier Proteins
• Dietary Fats
• Enzyme Inhibitors
• PPAR alpha
• Receptors, LDL
• Srebf1 protein, mouse
• Sterol Regulatory Element Binding Protein 1
• Triglycerides
• microsomal triglyceride transfer protein
• Cholesterol
• Ezetimibe
• Acarbose

Topics

• Acarbose (pharmacology, therapeutic use)
• Animals
• Anticholesteremic Agents (pharmacology, therapeutic use)
• Azetidines (pharmacology, therapeutic use)
• Carrier Proteins (metabolism)
• Cholesterol (metabolism)
• Dietary Fats (adverse effects)
• Disease Models, Animal
• Drug Therapy, Combination
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Ezetimibe
• Fatty Liver (drug therapy, etiology, metabolism)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis (drug therapy, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• PPAR alpha (metabolism)
• Receptors, LDL (metabolism)
• Sterol Regulatory Element Binding Protein 1 (metabolism)
• Triglycerides (metabolism)