Quantitative Profiling of Hydroxy Lipid Metabolites in Mouse Organs Reveals Distinct Lipidomic Profiles and Modifications Due to Elevated n-3 Fatty Acid Levels.
Polyunsaturated fatty acids (PUFA) are precursors of bioactive metabolites and mediators. In this study, the profile of hydroxyeicosatetraenoic (HETE), hydroxyeicosapentaenoic (HEPE) and hydroxydocosahexaenoic (HDHA) acids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in colon, liver, lung, spleen, muscle, heart and kidney tissue of healthy wildtype mice were characterized, and compared to profiles in organs from transgenic fat-1 mice engineered to express theCaenorhabditis elegansfat-1 gene encoding an n-3 desaturase and thereby with endogenously elevated n-3 PUFA levels. PUFAs were measured using gas chromatography. The lipid metabolites were assayed using LC-MS/MS. AA and DHA were the prominent PUFAs in wildtype and fat-1 mice. EPA levels were low in both groups even though there was a significant increase in fat-1 organs with an up to 12-fold increase in fat-1 spleen and kidney. DHA levels increased by approximately 1.5-fold in fat-1 as compared to wildtype mice. While HETEs remained the same or decreased moderately and HDHAs increased 1- to 3-fold, HEPE formation in fat-1 tissues increased from 8- (muscle) to 44-fold (spleen). These findings indicate distinct profiles of monohydroxy lipid metabolites in different organs and strong utilization of EPA for HEPE formation, by which moderate EPA supplementation might trigger formation of biologically active EPA-derived resolvins.
Department of Medicine, Division of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany. Cheng-Ying.Chiu@charite.de.|Lipid Clinic, Experimental and Clinical Research Centre (ECRC), Charité University Medicine and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany. Cheng-Ying.Chiu@charite.de.
Cheng-Ying
CY
Chiu
Department of Medicine, Division of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany. christopher.smyl@charite.de.|Lipid Clinic, Experimental and Clinical Research Centre (ECRC), Charité University Medicine and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany. christopher.smyl@charite.de.
Christopher
C
Smyl
Lipidomix, 13125 Berlin, Germany. inci.dogan@lipidomix.de.
Inci
I
Dogan
Lipidomix, 13125 Berlin, Germany. michael.rothe@lipidomix.de.
Michael
M
Rothe
Department of Medicine, Division of Hepatology and Gastroenterology, Charité University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany. karsten.weylandt@charite.de.|Lipid Clinic, Experimental and Clinical Research Centre (ECRC), Charité University Medicine and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany. karsten.weylandt@charite.de.
Karsten-H
KH
Weylandt
HDHA; HEPE; HETE; arachidonic acid; docosahexaenoic acid; eicosapentaenoic acid; fat-1; omega-3; omega-6; polyunsaturated fatty acids