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

被引：21

作者：

Gowda, Siddabasave Gowda B. ^{[1
]}

Tsukui, Takayuki ^{[2
]}

Fuda, Hirotoshi ^{[1
]}

Minami, Yusuke ^{[1
]}

Gowda, Divyavani ^{[1
]}

Chiba, Hitoshi ^{[2
]}

Hui, Shu-Ping ^{[1
]}

机构：

[1] Hokkaido Univ, Fac Hlth Sci, Kita Ku, Kita 12,Nishi 5, Sapporo, Hokkaido 0600812, Japan

[2] Sapporo Univ Hlth Sci, Dept Nutr, Higashi Ku, Nakanuma Nishi 4-3-1-15, Sapporo, Hokkaido 0070894, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 14期

关键词：

FAHFAs; DHA; NRF2; lipid droplet; HRMS; LC; MS; FAHFAS;

D O I：

10.3390/ijms22147598

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：13

共 24 条

[21] Discovery of a Class of Endogenous Mammalian Lipids with Anti-Diabetic and Anti-inflammatory Effects [J].

Yore, Mark M. ;

Syed, Ismail ;

Moraes-Vieira, Pedro M. ;

Zhang, Tejia ;

Herman, Mark A. ;

Homan, Edwin A. ;

Patel, Rajesh T. ;

Lee, Jennifer ;

Chen, Shili ;

Peroni, Odile D. ;

Dhaneshwar, Abha S. ;

Hammarstedt, Ann ;

Smith, Ulf ;

McGraw, Timothy E. ;

Saghatelian, Alan ;

Kahn, Barbara B. .

CELL, 2014, 159 (02) :318-332

[22] Omega-3 polyunsaturated fatty acids improve the antioxidative defense in rat astrocytes via an Nrf2-dependent mechanism [J].

Zgorzynska, Emilia ;

Dziedzic, Barbara ;

Gorzkiewicz, Anna ;

Stulczewski, Dawid ;

Bielawska, Katarzyna ;

Su, Kuan-Pin ;

Walczewska, Anna .

PHARMACOLOGICAL REPORTS, 2017, 69 (05) :935-942

[23] PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms [J].

Zhou, Peng ;

Santoro, Anna ;

Peroni, Odile D. ;

Nelson, Andrew T. ;

Saghatelian, Alan ;

Siegel, Dionicio ;

Kahn, Barbara B. .

JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (10) :4138-4150

[24] Comprehensive Screening and Identification of Fatty Acid Esters of Hydroxy Fatty Acids in Plant Tissues by Chemical Isotope Labeling Assisted Liquid Chromatography-Mass Spectrometry [J].

Zhu, Quan-Fei ;

Yan, Jing-Wen ;

Zhang, Tian-Yi ;

Xiao, Hua-Ming ;

Feng, Yu-Qi .

ANALYTICAL CHEMISTRY, 2018, 90 (16) :10056-10063

← 1 2 3 →