Dietary ferulic acid suppresses body fat accumulation via induction of beige adipocyte formation and cyclodextrin inclusion ferulic acid improves bioavailability in mice

Background and objective: It has been reported that dietary ferulic acid (FA) significantly suppressed body fat accumulation, despite its poorly soluble in water and low oral bioavailability [1]. However, molecular mechanism of this effect remains unclear. We hypothesized that anti-obesity by dietary FA is due to induction of beige adipocyte formation. In addition, highly water soluble and bioavailable FA formulation would be able to obtain FA-mediated various biological function even at low doses. Several reports indicated that cyclodextrin (CD) inclusion complex can enhance its oral bioavailability [2]. Therefore, CD inclusion FA (CD-FA) can be expected to induce beige adipocyte formation even at low doses. According to these backgrounds, the aim of this study is to demonstrate induction of beige adipocyte formation by dietary FA, evaluation of bioavailability of CD-FA, and dietary CD-FA-mediated beige adipocyte formation at low doses. Methods: 1) Five-week-old male C57BL/6J mice were assigned to four different groups: control diet group, control diet supplemented with 0.2, 0.5, or 1.0 % FA groups (0.2FA, 0.5FA and 1.0FA) for 4 weeks. After 4 weeks, blood and adipose tissue samples were collected. 2) Mice received single oral doses of native FA or CD-FA by intragastric intubation. Blood and inguinal white adipose tissue (iWAT) samples were collected at 15, 30, 60, 120 and 240 min after loading. FA concentration in plasma and iWAT were determined. Results: Overall weight gain as well as WAT weight significantly decreased in the 1.0FA group relative to the control. Dietary FA (0.5 and 1.0FA groups) significantly induced beige adipocyte formation in iWAT in mice. Both total (free and conjugated form) and free form of FA in plasma concentration were significantly elevated after CD-FA compared with these of native FA. Conclusions: Dietary FA significantly induces beige adipocyte formation in iWAT and contributes suppression of body fat accumulation. CD-FA significantly improves low bioavailability of native FA. We are continuing to examine whether CD-FA induces beige adipocyte formation even at low doses.