Serum Metabolomics Uncovers the Mechanisms of Inulin in Preventing Non-Alcoholic Fatty Liver Disease

Abstract

Inulin may be a promising therapeutic molecule for treating non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its therapeutic activity remain unclear. To address this issue, a high-fat-diet-induced NAFLD mouse model was developed and treated with inulin. The NAFLD phenotype was evaluated via histopathological analysis and biochemical parameters, including serum levels of alanine aminotransferase, aspartate aminotransferase, liver triglycerides, etc. A serum metabolomics study was conducted using ultra-performance liquid chromatography coupled with tandem mass spectrometry. The results revealed that inulin mitigated NAFLD symptoms such as histopathological changes and liver cholesterol levels. Through the serum metabolomics study, 347 differential metabolites were identified between the model and control groups, and 139 differential metabolites were identified between the inulin and model groups. Additionally, 48 differential metabolites (such as phosphatidylserine, dihomo-γ-linolenic acid, L-carnitine, and 13-HODE) were identified as candidate targets of inulin and subjected to pathway enrichment analysis. The results revealed that these 48 differential metabolites were enriched in several metabolic pathways such as fatty acid biosynthesis and cardiolipin biosynthesis. Taken together, our results suggest that inulin might attenuate NAFLD partially by modulating 48 differential metabolites and their correlated metabolic pathways, constituting information that might help us find novel therapies for NAFLD.