Abstract
Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.
Highlights
Excessive high fat diet consumption increases serum free fatty acids (FFA) and cholesterol which is known as primary factor leading to high lipid deposition in the liver and eventually cause hepatic s teatosis[1]
Principal Component Analysis (PCA) of palm kernel oil (PKO) against high-fat diet (HFD) generated a total of 20,832 peaks in positive mode with average of 2604 peaks per sample
This study reported untargeted metabolomic analysis of enhanced formulation of tocotrienol-rich fraction (TRF) (ETRF) supplementation in mice fed with HFD (60% kcal from fat) using the genetically modified B6.Cg-LepOb/J strain
Summary
Excessive high fat diet consumption increases serum free fatty acids (FFA) and cholesterol which is known as primary factor leading to high lipid deposition in the liver and eventually cause hepatic s teatosis[1]. Glucagon-like peptide-1 (GLP-1) receptor agonist[7], sodium-glucose co-transporter 2 (SGLT2) inhibitors[8] and thiazolidinediones[9] Lipid lowering agents such as s tatins[10] and nuclear receptors drugs such as ursodeoxycholic acid (UCDA)[11] and obeticholic acid (OCA)[12] are other choices included as a treatment for NAFLD. Metformin and GLP-1 induce diarrhoea[13,14] while thiazolidinediones induce weight gain[15] Other agents such as statins, UCDA and OCA have proven ineffective in treating NAFLD and far more suitable for N ASH10,16,17. Supplementation with tocotrienol for 12 weeks in NAFLD patients reported significant improvement of liver profile and inflammatory markers but liver echogenic findings remained unchanged[19]. MCT has shown to be readily absorbed and transported directly into the liver through the portal vein to be further metabolised[29,30,31]
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