Nrf2-mediated antioxidant defense and peroxiredoxin 6 are linked to biosynthesis of palmitic acid ester of 9-hydroxystearic acid

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Item Type:	Article
Title:	Nrf2-mediated antioxidant defense and peroxiredoxin 6 are linked to biosynthesis of palmitic acid ester of 9-hydroxystearic acid
Creators Name:	Kuda, O., Brezinova, M., Silhavy, J., Landa, V., Zidek, V., Dodia, C., Kreuchwig, F., Vrbacky, M., Balas, L., Durand, T., Hübner, N., Fisher, A.B., Kopecky, J. and Pravenec, M.
Abstract:	Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising anti-diabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) vialipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, QTL mapping and correlation analyses in rat BXH/HXB recombinant inbred strains, and response to oxidative stress in murine models, we elucidated the potential pathway of biosynthesis of several FAHFAs.Comprehensive analysis of WAT samples identified ∼160 regioisomers documenting the complexity of this lipid class. The linkage analysis highlighted several members of Nuclear factor, erythroid 2-like 2 ()-mediated antioxidant defense system (), lipid-handling proteins () and family of Flavin Containing Monooxygenase () as the positional candidate genes. Transgenic expression ofand deletion ofgenes resulted in reduction of palmitic acid ester of 9-hydroxystearic acid (9-PAHSA) and 11-PAHSA levels, while oxidative stress induced by an inhibitor of glutathione synthesis increased PAHSA levels nonspecifically.Our results indicate that the synthesis of FAHFAscarbohydrate-responsive element-binding protein (ChREBP)-drivenlipogenesis depends on the adaptive antioxidant system and suggest that FAHFAs may link activity of this system with insulin sensitivity in peripheral tissues.
Keywords:	Biomarkers, Enzymologic Gene Expression Regulation, Esters, Gene Expression Profiling, Inbred BN Rats, Inbred C57BL Mice, Inbred SHR Rats, Knockout Mice, Metabolomics, NF-E2-Related Factor 2, Oxidative Stress, Palmitic Acid, Peroxiredoxin VI, Random Allocation, Stearic Acids, Transgenic Rats, White Adipose Tissue, Animals, Mice, Rats
Source:	Diabetes
ISSN:	0012-1797
Publisher:	American Diabetes Association
Volume:	67
Number:	6
Page Range:	1190-1199
Date:	June 2018
Official Publication:	https://doi.org/10.2337/db17-1087
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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