Nrf2-Mediated Antioxidant Defense and Peroxiredoxin 6 Are Linked to Biosynthesis of Palmitic Acid Ester of 9-Hydroxystearic Acid
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
P30 ES013508
NIEHS NIH HHS - United States
PubMed
29549163
PubMed Central
PMC6463562
DOI
10.2337/db17-1087
PII: db17-1087
Knihovny.cz E-zdroje
- MeSH
- bílá tuková tkáň enzymologie metabolismus MeSH
- biologické markery metabolismus MeSH
- estery chemie metabolismus MeSH
- faktor 2 související s NF-E2 genetika metabolismus MeSH
- krysa rodu Rattus MeSH
- kyselina palmitová chemie metabolismus MeSH
- kyseliny stearové chemie metabolismus MeSH
- metabolomika metody MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- náhodné rozdělení MeSH
- oxidační stres * MeSH
- peroxiredoxin VI genetika metabolismus MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- regulace genové exprese enzymů * MeSH
- stanovení celkové genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 9-hydroxystearic acid MeSH Prohlížeč
- biologické markery MeSH
- estery MeSH
- faktor 2 související s NF-E2 MeSH
- kyselina palmitová MeSH
- kyseliny stearové MeSH
- Nfe2l2 protein, mouse MeSH Prohlížeč
- Nfe2l2 protein, rat MeSH Prohlížeč
- peroxiredoxin VI MeSH
- Prdx6 protein, mouse MeSH Prohlížeč
Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising antidiabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) via de novo lipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, quantitative trait locus mapping, and correlation analyses in rat BXH/HXB recombinant inbred strains, as well as 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 the nuclear factor, erythroid 2 like 2 (Nrf2)-mediated antioxidant defense system (Prdx6, Mgst1, Mgst3), lipid-handling proteins (Cd36, Scd6, Acnat1, Acnat2, Baat), and the family of flavin containing monooxygenases (Fmo) as the positional candidate genes. Transgenic expression of Nrf2 and deletion of Prdx6 genes 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 FAHFAs via carbohydrate-responsive element-binding protein-driven de novo lipogenesis depends on the adaptive antioxidant system and suggest that FAHFAs may link activity of this system with insulin sensitivity in peripheral tissues.
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