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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #354476
Title: Blood levels of endocannabinoids, oxylipins, and metabolites are altered in hemodialysis patients

Author
item WATKINS, BRUCE - University Of California, Davis
item FRIEDMAN, ALLON - Indiana University
item KIM, JEFFREY - University Of California, Davis
item BORKOWSKI, KAMIL - University Of California, Davis
item KAISER, SHAUN - Texas Kidney Institute
item FIEHN, OLIVER - University Of California, Davis
item Newman, John

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2022
Publication Date: 8/29/2022
Citation: Watkins, B.A., Friedman, A.N., Kim, J., Borkowski, K., Kaiser, S., Fiehn, O., Newman, J.W. 2022. Blood levels of endocannabinoids, oxylipins, and metabolites are altered in hemodialysis patients. International Journal of Molecular Sciences. 23(17). https://doi.org/10.3390/ijms23179781.
DOI: https://doi.org/10.3390/ijms23179781

Interpretive Summary: Hemodialysis patients (HDP) typically have elevated cardiovascular disease risk and associated biomarkers including high blood pressure, a greater incidence of chronic inflammation and inflammatory markers, as compared to healthy subjects. HDP also often show low plasma levels of long chain n-3polyunsaturated fatty acids (PUFA). The primary aim of this investigation was to compare HDP and healthy matched control women by the levels of two classes of inflammatory mediators, namely the endocannabinoids and oxylipins, as well as by their global plasma metabolomic profiles. Plasma red blood cell plasma fatty acids were analyzed by GC and plasma was analyzed using ultra performance liquid chromatography followed by electrospray ionization and tandem MS for endocannabinoids and oxylipins. Global untargeted metabolite profiling of plasma was performed on GCTOF MS platform. HDP showed lower levels of eicosapentaenoic acid its oxylipin metabolites 5-hydroxypenaenoic acid (HEPE), 12-HEPE, 14,15-dihydroxyeicosatetraenoic acid (DiHETE), 17,18-DiHETE and 17(18)-epoxyeicosatretraenoic acid in plasma compared to controls. The docosahexaenoic acid 19(20)-epoxydocosahexaenoic acid was also lower in the HDP compared to the healthy controls. The reduced epoxy fatty acids in HDP may be in part responsible for the reduced peripheral vascular relaxation generally observed in hemodialysis patients. Further, the levels of 2-oleoylglycerol, 1-linoleoylglycerol and 2-linoleoylglyecrol were higher in female HDP compared to the healthy controls. From the global plasma metabolite analysis, the levels of kynurenine, citrulline and creatine were higher in HDP compared to the healthy controls, as would be expected in subjects with impaired renal function. In general prominent differences in amino acid metabolism and the intermediates of the uric acid cycle were observed. This study provides new information regarding changes in endocannabinoid and oxylipin metabolite profiles in the plasma of women on hemodialysis, providing new hypotheses regarding the role of dietary PUFAs in subjects with advancing kidney disease.

Technical Abstract: Hemodialysis patients (HDP) have high blood pressure, greater incidence of chronic inflammation, higher C-reactive protein and risk for cardiovascular disease compared to healthy subjects. Typically HDP demonstrate unusually low plasma n-3 PUFA levels. The purpose of our investigation was to characterize the endocannabinoids and oxylipins in female HDP and female healthy matched controls. Plasma RBC and plasma fatty acids were analyzed by GC and plasma was extracted and subsequently analyzed using ultra performance liquid chromatography followed by electrospray ionization and tandem MS for endocannabinoids and oxylipins. Global untargeted metabolite profiling of plasma was performed on GCTOF MS platform. HDP showed lower EPA and family related oxylipins 5- and 12-HEPE and 14-15- and 17,18-DiHETE in plasma compared to controls. The potent n-3 vasodilators 17(18)-EpETrE and 19(20)-EpDPE were lower in the HDP compared to the healthy controls raising the possibility that hypertension in HDP could in part be due to reduced peripheral vascular relaxation. Further, the levels of 2-OG, 1-LG and 2-LG were higher in female HDP compared to the healthy controls. From the global plasma metabolite analysis of plasma, the levels of kynurenine, citrulline and creatine were higher in female HDP compared to the female healthy controls. In general prominent differences in amino acid metabolism and the intermediates of the uric acid cycle were observed. Herein, we report novel findings on endocannabinoids and oxylipins in female HDP that demonstrate differences compared to controls. This research will provide new opportunities to evaluate the role of dietary PUFA in clinical disease in kidney dialysis patients.