Tocotrienol-rich fraction in medium-chain triglyceride carrier upregulates purine metabolism in non-alcoholic fatty liver disease (NAFLD) animal model

Abstract

Abstract Background Non-alcoholic fatty liver disease (NAFLD) has been associated with metabolic syndrome (MetS). One of the underlying mechanisms of NAFLD is an aberration in amino acid metabolism and signalling. The tocotrienol-rich fraction (TRF) has been shown to improve NAFLD and is thus recommended as a supplement in NAFLD. However, TRF often exhibits low bioavailability. Recently, our group reported that TRF with medium-chain triglyceride (MCT) carriers could potentially improve steatosis, bile acid metabolism, lipid, and fatty acid metabolism. Objective This study investigated the effects of TRF-MCT on amino acid metabolism in an NAFLD mice model. Methods Male B6.Cg-LepOb/J mice were used as an NAFLD mouse model and randomly divided into three groups: high-fat diet only (HFD), TRF-MCT, and palm kernel oil (PKO) (vehicle MCT). After 6 weeks of supplementation, serum was collected for untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS), significant metabolic features were annotated to determine the fold change (FC), and analysis was performed (SIMCA and MetaboAnalyst). Results In the TRF-MCT group, 11 amino acids were annotated. Urocanic acid group (FC = 1.0146), ascorbic acid 2-sulphate (FC = 0.81939), 3-isoproprylmalic acid (FC = 0.66469), and 6-methylnicotamide (FC = 0.6507) were the most upregulated (p < 0.05). Lysine (FC = − 0.88836), leucine (FC = − 0.7949), pyridoxamine (FC = − 0.76347), 3-indoxyl sulphate (FC = − 0.73989), threonine (FC = − 0.66945), and indolelactic acid (FC = − 0.61605) were the most downregulated (p < 0.05). Glutamic acid (FC = 0.79069) levels were upregulated in the PKO-treated group compared to the HFD group (p < 0.05). Conclusion TRF-MCT-supplemented NAFLD mouse model shown an altered amino acid which involves in valine, leucine, and isoleucine biosynthesis, aminoacyl-transfer RNA (aminoacyl-tRNA) biosynthesis, and vitamin B6 metabolism. Thus, suggesting TRF-MCT has a protective effect and repairing activities in the liver of the NAFLD mouse model.

Keywords

• Non-alcoholic fatty liver disease
• Tocotrienol-rich fraction
• Medium-chain triglycerides
• Untargeted metabolomics
• Amino acids