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Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2

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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
lipid droplet
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
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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