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Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2
| Title: | Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2 |
| Authors: | Gowda, Siddabasave Gowda B. Browse this author →KAKEN DB | | Tsukui, Takayuki Browse this author | | Fuda, Hirotoshi Browse this author →KAKEN DB | | Minami, Yusuke Browse this author | | Gowda, Divyavani Browse this author | | Chiba, Hitoshi Browse this author | | Hui, Shu-Ping Browse this author →KAKEN DB |
| Keywords: | FAHFAs | | DHA | | NRF2 | | lipid droplet | | HRMS | | LC | | MS |
| Issue Date: | Jul-2021 |
| Publisher: | MDPI |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 22 |
| Issue: | 14 |
| Start Page: | 7598 |
| Publisher DOI: | 10.3390/ijms22147598 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82490 |
| Appears in Collections: | 保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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