Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers
Abstract Oxylipins are metabolites of polyunsaturated fatty acids that mediate cardiovascular health by attenuation of inflammation, vascular tone, hemostasis, and thrombosis. Very low‐density lipoproteins (VLDL) contain oxylipins, but it is unknown whether the liver regulates their concentrations....
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doaj-b61183b5f3de4a8ab1efd006ff41281e2021-02-25T15:10:30ZengWileyPhysiological Reports2051-817X2021-02-0194n/an/a10.14814/phy2.14480Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat liversRachel E. Walker0Olga V. Savinova1Theresa L. Pedersen2John W. Newman3Gregory C. Shearer4Department of Nutritional Sciences The Pennsylvania State University University Park PA USADepartment of Biomedical Sciences New York Institute of Technology College of Osteopathic Medicine Old Westbury NY USAAdvanced Analytics Davis CA USADepartment of Food Science and Technology University of California Davis CA USADepartment of Nutritional Sciences The Pennsylvania State University University Park PA USAAbstract Oxylipins are metabolites of polyunsaturated fatty acids that mediate cardiovascular health by attenuation of inflammation, vascular tone, hemostasis, and thrombosis. Very low‐density lipoproteins (VLDL) contain oxylipins, but it is unknown whether the liver regulates their concentrations. In this study, we used a perfused liver model to observe the effect of inflammatory lipopolysaccharide (LPS) challenge and soluble epoxide hydrolase inhibition (sEHi) on VLDL oxylipins. A compartmental model of deuterium‐labeled linoleic acid and palmitic acid incorporation into VLDL was also developed to assess the dependence of VLDL oxylipins on fatty acid incorporation rates. LPS decreased the total fatty acid VLDL content by 30% [6%,47%], and decreased final concentration of several oxylipins by a similar amount (13‐HOTrE, 35% [4%,55%], −1.3 nM; 9(10)‐EpODE, 29% [3%,49%], −2.0 nM; 15(16)‐EpODE, 29% [2%,49%], −1.6 nM; AA‐derived diols, 32% [5%,52%], −2.4 nM; 19(20)‐DiHDPA, 31% [7%,50%], −1.0 nM). However, the EPA‐derived epoxide, 17(18)‐EpETE, was decreased by 75% [49%,88%], (−0.52 nM) with LPS, double the suppression of other oxylipins. sEHi increased final concentration of DHA epoxide, 16(17)‐EpDPE, by 99% [35%,193%], (2.0 nM). Final VLDL‐oxylipin concentrations with LPS treatment were not correlated with linoleic acid kinetics, suggesting they were independently regulated under inflammatory conditions. We conclude that the liver regulates oxylipin incorporation into VLDL, and the oxylipin content is altered by LPS challenge and by inhibition of the epoxide hydrolase pathway. This provides evidence for delivery of systemic oxylipin signals by VLDL transport.https://doi.org/10.14814/phy2.14480compartmental modelingfatty acid/metabolismlipoproteinsperfusionpolyunsaturated fatty acidssoluble epoxide hydrolase inhibitor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachel E. Walker Olga V. Savinova Theresa L. Pedersen John W. Newman Gregory C. Shearer |
spellingShingle |
Rachel E. Walker Olga V. Savinova Theresa L. Pedersen John W. Newman Gregory C. Shearer Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers Physiological Reports compartmental modeling fatty acid/metabolism lipoproteins perfusion polyunsaturated fatty acids soluble epoxide hydrolase inhibitor |
author_facet |
Rachel E. Walker Olga V. Savinova Theresa L. Pedersen John W. Newman Gregory C. Shearer |
author_sort |
Rachel E. Walker |
title |
Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers |
title_short |
Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers |
title_full |
Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers |
title_fullStr |
Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers |
title_full_unstemmed |
Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers |
title_sort |
effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers |
publisher |
Wiley |
series |
Physiological Reports |
issn |
2051-817X |
publishDate |
2021-02-01 |
description |
Abstract Oxylipins are metabolites of polyunsaturated fatty acids that mediate cardiovascular health by attenuation of inflammation, vascular tone, hemostasis, and thrombosis. Very low‐density lipoproteins (VLDL) contain oxylipins, but it is unknown whether the liver regulates their concentrations. In this study, we used a perfused liver model to observe the effect of inflammatory lipopolysaccharide (LPS) challenge and soluble epoxide hydrolase inhibition (sEHi) on VLDL oxylipins. A compartmental model of deuterium‐labeled linoleic acid and palmitic acid incorporation into VLDL was also developed to assess the dependence of VLDL oxylipins on fatty acid incorporation rates. LPS decreased the total fatty acid VLDL content by 30% [6%,47%], and decreased final concentration of several oxylipins by a similar amount (13‐HOTrE, 35% [4%,55%], −1.3 nM; 9(10)‐EpODE, 29% [3%,49%], −2.0 nM; 15(16)‐EpODE, 29% [2%,49%], −1.6 nM; AA‐derived diols, 32% [5%,52%], −2.4 nM; 19(20)‐DiHDPA, 31% [7%,50%], −1.0 nM). However, the EPA‐derived epoxide, 17(18)‐EpETE, was decreased by 75% [49%,88%], (−0.52 nM) with LPS, double the suppression of other oxylipins. sEHi increased final concentration of DHA epoxide, 16(17)‐EpDPE, by 99% [35%,193%], (2.0 nM). Final VLDL‐oxylipin concentrations with LPS treatment were not correlated with linoleic acid kinetics, suggesting they were independently regulated under inflammatory conditions. We conclude that the liver regulates oxylipin incorporation into VLDL, and the oxylipin content is altered by LPS challenge and by inhibition of the epoxide hydrolase pathway. This provides evidence for delivery of systemic oxylipin signals by VLDL transport. |
topic |
compartmental modeling fatty acid/metabolism lipoproteins perfusion polyunsaturated fatty acids soluble epoxide hydrolase inhibitor |
url |
https://doi.org/10.14814/phy2.14480 |
work_keys_str_mv |
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