Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2 |
| |
| Authors: | Siddabasave Gowda B. Gowda Takayuki Tsukui Hirotoshi Fuda Yusuke Minami Divyavani Gowda Hitoshi Chiba Shu-Ping Hui |
| |
| Affiliation: | 1.Faculty of Health Sciences, Hokkaido University, Kita 12, Nishi 5, Kita-ku, Sapporo 060-0812, Japan; (S.G.B.G.); (H.F.); (Y.M.); (D.G.);2.Department of Nutrition, Sapporo University of Health Sciences, Nakanuma Nishi-4-3-1-15, Higashi-ku, Sapporo 007-0894, Japan; (T.T.); (H.C.) |
| |
| Abstract: | Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. Herein, we examined for the first time the synthetic docosahexaenoic acid esters of 12-hydroxy stearic acid (12-DHAHSA) or oleic acid (12-DHAHOA) against NRF2 activation in cultured human hepatoma-derived cells (C3A). The effect of DHA-derived FAHFAs on lipid metabolism was explored by the nontargeted lipidomic analysis using liquid chromatography-mass spectrometry. Furthermore, their action on lipid droplet (LD) oxidation was investigated by the fluorescence imaging technique. The DHA-derived FAHFAs showed less cytotoxicity compared to their native fatty acids and activated the NRF2 in a dose-dependent pattern. Treatment of 12-DHAHOA with C3A cells upregulated the cellular triacylglycerol levels by 17-fold compared to the untreated group. Fluorescence imaging analysis also revealed the suppression of the degree of LDs oxidation upon treatment with 12-DHAHSA. Overall, these results suggest that DHA-derived FAHFAs as novel and potent activators of NRF2 with plausible antioxidant function. |
| |
| Keywords: | FAHFAs DHA NRF2 lipid droplet HRMS LC/MS |
|
|
