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.
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.
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.
Combination therapy with EZ and AC for 24 weeks improved the histopathological findings
in a mouse model of NAFLD.