Oxylipins are oxygenated metabolites of fatty acids that share several similar biochemical characteristics and functions to fatty acids including transport and trafficking. Oxylipins are most commonly measured in the non-esterified form which can be found in plasma, free or bound to albumin. The non-esterified form, however, reflects only one of the possible pools of oxylipins and is by far the least abundant circulating form of oxylipins. Further, this fraction cannot reliably be extrapolated to the other, more abundant, esterified pool. In cells too, esterified oxylipins are the most abundant form, but are seldom measured and their potential roles in signaling are not well established. In this review, we examine the current literature on experimental oxylipin measurements to describe the lack in reporting the esterified oxylipin pool. We outline the metabolic and experimental importance of esterified oxylipins using well established roles of fatty acid trafficking in non-esterified fatty acids and in esterified form as components of circulating lipoproteins. Finally, we use mathematical modeling to simulate how exchange between cellular esterified and unesterified pools would affect intracellular signaling.. The explicit inclusion of esterified oxylipins along with the non-esterified pool has the potential to convey a more complete assessment of the metabolic consequences of oxylipin trafficking.
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http://dx.doi.org/10.3390/metabo12111007 | DOI Listing |
J Lipid Res
January 2025
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Graz, Austria; Field of Excellence BioHealth - University of Graz, Graz, Austria. Electronic address:
Phospholipids containing oxidized esterified PUFA residues (OxPLs) are increasingly recognized for multiple biological activities and causative involvement in disease pathogenesis. Pharmacokinetics of these compounds in blood plasma is essentially not studied. Human plasma contains both genuine phospholipases A (PAF-AH (also called Lp-PLA) and sPLA) and multifunctional enzymes capable of removing sn-2 residues in native and oxidized PLs (LCAT, PRDX6).
View Article and Find Full Text PDFProstaglandins Leukot Essent Fatty Acids
December 2024
Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, , Netherlands. Electronic address:
Lipid dyshomeostasis and neuroinflammation are key hallmarks of neuropsychiatric and neurodegenerative disorders, including major depressive disorder and Alzheimer's disease. In particular, polyunsaturated fatty acids (PUFAs) and their derivatives called oxylipins gained specific interest in this context, especially considering their capacity to orchestrate neuroinflammatory responses via direct modulation of microglia. The hippocampus and hypothalamus are crucial brain regions for regulating mood and cognition that are implicated in a variety of neuropsychiatric and neurodegenerative disorders and there is ample evidence for the sex-bias in risks for the development as well as sex-bias in the presentation of such psychiatric diseases, including the neuroinflammatory response.
View Article and Find Full Text PDFJ Pharm Biomed Anal
November 2024
Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, 28660 Boadilla del Monte, Madrid, Spain. Electronic address:
Oxylipins are signaling lipids derived from the oxidation of polyunsaturated fatty acids (PUFAs). In lipidomic studies, human plasma may be subjected to various storage conditions and freeze-thaw cycles, which may impact the analysis of these compounds. In this study, we used liquid chromatography coupled with mass spectrometry (LC-MS) to examine the influence of up to five freeze-thaw cycles (FTCs) on free and total (mostly esterified) oxylipins in human plasma and the influence of temperature and storage duration (4 °C for up to 120 h and -20 °C and -80 °C for 1-98 days) in the presence or absence of butylated hydroxytoluene (BHT) on extracted oxylipins stored in LC-MS amber vials.
View Article and Find Full Text PDFJ Nutr
December 2024
Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada; Canadian Centre for Agri-Food Research in Health and Medicine (CCARM), Winnipeg, MB, Canada. Electronic address:
Background: The dietary requirement for α-linolenic acid (ALA) remains unclear, as evidenced by the absence of a Recommended Dietary Allowance (RDA) for this essential fatty acid (FA). In previous studies, we observed that the amount of dietary ALA required to maximize nonesterified (NE) DHA oxylipins appears to be higher than the amount required to maximize tissue esterified DHA, which have classically been used to estimate the ALA requirement. Further, we observed that dietary ALA reduces esterified arachidonic acid (ARA) and its NE oxylipins.
View Article and Find Full Text PDFmedRxiv
September 2024
Department of Surgery, City of Hope, Duarte CA 91010.
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