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

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. and Brezinova, M. and Silhavy, J. and Landa, V. and Zidek, V. and Dodia, C. and Kreuchwig, F. and Vrbacky, M. and Balas, L. and Durand, T. and Hübner, N. and Fisher, A.B. and 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
Publisher:American Diabetes Association
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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