Ferulic acid maintains the self-renewal capacity of embryo stem cells and adipose-derived mesenchymal stem cells in high fat diet-induced obese mice.

Self-renewal is required for embryo stem cells (ESCs) and adipose-derived mesenchymal stem cells (ADMSCs). This study examined the ability of ferulic acid in mouse ESCs and ADMSCs, in a high fat diet-induced mouse model. Initially, five natural compounds of ferulic acid, xanthohumol, curcumin, ascorbic acid, and quercetin were screened in ESCs using an alkaline phosphate ⁺(AP⁺) assay, as a self-renewal biomarker. A ferulic acid treatment was the highest AP⁺ staining in hop-hit screening compounds. Also a ferulic acid increased Nanog mRNA levels in ESCs. The in vivo effects of ferulic acid were next examined in an obese mouse model. C57BL/6 J male mice were fed either a high fat diet (HFD) or control diet with ferulic acid (5 g/kg diet) for 8 weeks. Ferulic acid exhibited weight loss and improved glucose homeostasis, lipid profiling, and hepatic steatosis in a HFD-induced mouse model. Next, ADMSCs (Sca-1⁺CD45^-), a hallmark of fat stem cells, were then isolated and quantified from mouse abdominal adipose tissue. A HFD decreased the Sca-1⁺CD45^- cell population of ADMSCs, but HFD-induced obese mice given ferulic acid showed an increased the Sca-1⁺CD45^- cell population of ADMSCs. Moreover, ferulic acid enhanced NANOG mRNA levels in human ADMSCs and its related gene mRNA expression. Overall, this study suggests that ferulic acid preserves self-renewal in ESCs, and contributes to ADMSCs self-renewal and effective weight control in obesity.