Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low‐density lipoproteins in isolated perfused rat livers
Open Access
- 24 February 2021
- journal article
- research article
- Published by Wiley in Physiological Reports
- Vol. 9 (4), e14480
- https://doi.org/10.14814/phy2.14480
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.Funding Information
- National Institutes of Health (7P20RR017662‐07, R56 HL131547, U24 DK097154)
- U.S. Department of Agriculture (2032‐51530‐022‐00D, 2032‐51530‐022‐25D)
This publication has 52 references indexed in Scilit:
- Type 2 Diabetes Associated Changes in the Plasma Non-Esterified Fatty Acids, Oxylipins and EndocannabinoidsPLOS ONE, 2012
- Experimental Endotoxemia Induces Adipose Inflammation and Insulin Resistance in HumansDiabetes, 2009
- Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biologyJournal of Lipid Research, 2009
- HDL is the major lipoprotein carrier of plasma F2-isoprostanesJournal of Lipid Research, 2009
- Arachidonic acid cytochrome P450 epoxygenase pathwayJournal of Lipid Research, 2009
- Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammationJournal of Lipid Research, 2009
- Lipoprotein lipase releases esterified oxylipins from very low-density lipoproteinsProstaglandins, Leukotrienes & Essential Fatty Acids, 2008
- Soluble Epoxide Hydrolase Inhibitors Reduce the Development of Atherosclerosis in Apolipoprotein E-Knockout Mouse ModelJournal of Cardiovascular Pharmacology, 2008
- Triglyceride-rich lipoprotein lipolysis increases aggregation of endothelial cell membrane microdomains and produces reactive oxygen speciesAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959