Inulin activates FXR-FGF15 signaling and further increases bile acids excretion in non-alcoholic fatty liver disease mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder defined as the presence of intrahepatic lipid deposition and steatosis as well as chronic inflammation without excessive alcohol consumption. Our previous studies found that inulin could dramatically improve lipid metabolism disorders in NAFLD murine models. In recent years, mounting evidence has approved that there are disproportionately increased bile acids (BAs) in patients with NAFLD while the hepatic bile acids signaling is suppressed. Meanwhile the primary function of bile acids is to promote the excretion of cholesterol and therefore keep the cholesterol metabolism balance. Hence, we investigate whether inulin exerts beneficial effects on lipid metabolism disorders by modulating bile acids signaling in our present study. And we found that inulin treatment significantly reversed the abnormal accumulation of bile acids in high-fat-induced NAFLD mice. Furthermore, our data confirmed that inulin supplementation attenuates NAFLD via restoring the activity of FXR accompanied by increasing hepatic bile acids de novo synthesis and further enhancing bile acids excretion in mice.