Palm-based tototrienol-rich fraction (TRF) supplementation modulates cardiac sod1 expression, fxr target gene expression and tauro-conjugated bile acid levels in aleptinemic mice fed a high-fat diet

Abstract

Abstract Tocotrienol-rich fraction (TRF) has been reported to protect the heart from oxidative stress-induced inflammation. It is, however, unclear whether the protective effects TRF against oxidative stress involve the activation of farnesoid-x receptor (fxr), a bile acid receptor, and the regulation of bile acid metabolites. In the current study, we investigated the effects of TRF supplementation on antioxidant activities, expression of fxr and its target genes in cardiac tissue, and serum untargeted metabolomics of high-fat diet-fed mice. Mice were divided into high-fat diet (HFD) with or without TRF supplementation (control) for six weeks. At the end of the intervention, weight (BW), waist circumference (WC), and random blood glucose were measured. Heart tissues were collected, and the gene expression of sod1, sod2, gpx and fxr and its target genes shp and stat3 was determined. Serum was subjected to untargeted metabolomic analysis using UHPLC-Orbitrap. In comparison to the control, the WC of the TRF-treated group was significantly higher (p > 0.05) than that of the HFD-only group, but there was no significant difference in weight or random blood glucose level. Downregulation of sod1, sod2 and gpx expression was observed in TRF-treated mice; however, only sod1 was significant when compared to the HFD only group. The expression of cardiac fxr and shp was significantly upregulated, but stat3 was significantly downregulated in the TRF-treated group compared to the HFD-only group. Biochemical pathways found to be influenced by TRF supplementation include bile acid secretion, primary bile acid biosynthesis, and biotin and cholesterol metabolism. In conclusion, TRF supplementation in HFD-fed mice affects antioxidant activities, and more interestingly, TRF also acts as a signaling molecule that is possibly involved in several bile acid-related biochemical pathways accompanied by an increase in cardiac fxr shp expression. This study provides new insight into TRF in deregulating bile acid receptors and metabolites in high-fat diet-fed mice.