TY - JOUR
T1 - Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low-density lipoproteins in isolated perfused rat livers
AU - Walker, Rachel E.
AU - Savinova, Olga V.
AU - Pedersen, Theresa L.
AU - Newman, John W.
AU - Shearer, Gregory C.
N1 - Publisher Copyright:
© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101564543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101564543&partnerID=8YFLogxK
U2 - 10.14814/phy2.14480
DO - 10.14814/phy2.14480
M3 - Article
C2 - 33625776
AN - SCOPUS:85101564543
SN - 2051-817X
VL - 9
JO - Physiological reports
JF - Physiological reports
IS - 4
M1 - e14480
ER -