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

Gowda, Siddabasave Gowda B.; Tsukui, Takayuki; Fuda, Hirotoshi et al.

International Journal of Molecular Sciences, 2021, 22(14), 7598

Permalink : https://hdl.handle.net/2115/82490

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https://doi.org/10.3390/ijms22147598     101

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アクセス権
open access
URI
https://hdl.handle.net/2115/82490
タイトル
Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2
著者
Gowda, Siddabasave Gowda B. ; Tsukui, Takayuki ; Fuda, Hirotoshi ; Minami, Yusuke ; Gowda, Divyavani ; Chiba, Hitoshi ; Hui, Shu-Ping
e-Rad_Researcher
50800504
著者名
Gowda, Siddabasave Gowda B.
著者名
Tsukui, Takayuki
e-Rad_Researcher
60576172
著者名
Fuda, Hirotoshi
著者名
Minami, Yusuke
著者名
Gowda, Divyavani
著者名
Chiba, Hitoshi
e-Rad_Researcher
90337030
著者名
Hui, Shu-Ping
言語
英語
キーワード
FAHFAs
DHA
NRF2
lipid droplet
HRMS
LC
MS
発行日
2021-07
出版者
MDPI
収録物名
International Journal of Molecular Sciences
巻(号)
22(14)
ページ
7598
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3390/ijms22147598