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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 #342065
Title: Abnormal lipoprotein oxylipins in metabolic syndrome and partial correction by omega-3 fatty acids

Author
item SHEARER, GREGORY - Pennsylvania State University
item BORKOWSKI, KAMIL - Pennsylvania State University
item PUUMALA, SUSAN - University Of South Dakota
item HARRIS, WILLIAM - Sanford Health
item Pedersen, Theresa
item Newman, John

Submitted to: Prostaglandins Leukotrienes and Essential Fatty Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/19/2017
Publication Date: 11/3/2017
Citation: Shearer, G.C., Borkowski, K., Puumala, S.L., Harris, W.S., Pedersen, T.L., Newman, J.W. 2017. Abnormal lipoprotein oxylipins in metabolic syndrome and partial correction by omega-3 fatty acids. Prostaglandins Leukotrienes and Essential Fatty Acids. 128:1-10. https://doi.org/10.1016/j.plefa.2017.10.006.
DOI: https://doi.org/10.1016/j.plefa.2017.10.006

Interpretive Summary: The Metabolic syndrome (MetSyn) is characterized by chronic inflammation which has been associated with an increased risk for cardiovascular and other diseases. A wide variety of fatty acids are metabolized by the body to create molecules that regulate inflammation, vascular biology, and many other processes. Oxylipins are a superclass of these lipid mediators formed by enzymes which introduce one or more molecules of oxygen into fatty acids. While the role oxylipins produced at the site of inflammation is well appreciated, the impact of those produced remotely and delivered to tissues is poorly understood. Most oxylipins in the blood stream are found along with most other lipids, as components of lipoprotein particles. If these circulating oxylipins can influence tissue processes, defective regulation of inflammation could be mediated by the elevated very low density lipoprotein (VLDL) and decreased high density lipoprotein (HDL) levels characteristic of MetSyn. MetSyn treatment with long chain omega-3 fatty acids has been shown to have beneficial effects on vascular risk factors in humans. The objective of this study was compare the VLDL, low density lipoprotein (LDL), and HDL oxylipin composition in 14 optimally healthy individuals and 31 MetSyn patients, and to determine how MetSyn subject consumption of 4g per day of pharmaceutical grade omega-3 fatty acids (P-OM3) for 16 weeks would the effect lipoprotein oxylipin profiles. Compared to healthy subjects, MetSyn is characterized by abnormalities of 1) pro-inflammatory, arachidonic acid-derived oxylipins from the lipoxygenase pathway in HDL; and 2) oxylipins mostly not derived from arachidonate in VLDL. P-OM3 treatment corrected many components of these abnormalities, reducing the burden of inflammatory mediators in circulating lipoproteins that could interfere with, or enhance, local effectors of inflammatory stress. We conclude that MetSyn is associated with a disruption of lipoprotein oxylipin patterns consistent with greater inflammatory stress, and the partial correction of these abnormal lipid mediator profiles by treatment with omega-3 fatty acids could explain some of the beneficial effects associated with this therapeutic strategy.

Technical Abstract: Metabolic syndrome (MetSyn) is characterized by chronic inflammation which mediates the associated high risk for cardiovascular and other diseases. Oxylipins are a superclass of lipid mediators with potent bioactivities in inflammation, vascular biology, and more. While their role as locally produced agents is appreciated, most oxylipins in plasma are found in lipoproteins suggesting defective regulation of inflammation could be mediated by the elevated VLDL and low HDL levels characteristic of MetSyn. Our objective was to compare the oxylipin composition of VLDL, LDL, and HDL in 14 optimally healthy individuals and 31 MetSyn patients, and then to determine the effects of treating MetSyn subjects with 4 g/day of prescription omega-3 fatty acids (P-OM3) on lipoprotein oxylipin profiles. We compared oxylipin compositions of healthy (14) and MetSyn (31) subjects followed by randomization and assignment to 4g/d P-OM3 for 16 weeks using LC/MS/MS. Compared to healthy subjects, MetSyn is characterized by abnormalities of 1) pro-inflammatory, arachidonate-derived oxylipins from the lipoxygenase pathway in HDL; and 2) oxylipins mostly not derived from arachidonate in VLDL. P-OM3 treatment corrected many components of these abnormalities, reducing the burden of inflammatory mediators within peripherally circulating lipoproteins that could interfere with, or enhance, local effectors of inflammatory stress. We conclude that MetSyn is associated with a disruption of lipoprotein oxylipin patterns consistent with greater inflammatory stress, and the partial correction of these dysoxylipinemias by treatment with omega-3 fatty acids could explain some of their beneficial effects