2024-03-29T05:29:34Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/824902022-11-17T02:08:08Zhdl_2115_35410hdl_2115_35409Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2Gowda, Siddabasave Gowda B.Tsukui, TakayukiFuda, HirotoshiMinami, YusukeGowda, DivyavaniChiba, HitoshiHui, Shu-PingFAHFAsDHANRF2lipid dropletHRMSLCMS490Fatty 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.MDPIJournal Articlehttp://hdl.handle.net/2115/82490International Journal of Molecular Sciences221475982021-07enginfo:doi/10.3390/ijms22147598none