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Prostaglandins Leukot Essent Fatty Acids. 2018 Jan;128:1-10. doi: 10.1016/j.plefa.2017.10.006. Epub 2017 Nov 11.

Abnormal lipoprotein oxylipins in metabolic syndrome and partial correction by omega-3 fatty acids.

Author information

1
Sanford Research, Sioux Falls, SD, USA; Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA; The Pennsylvania State University, Department of Nutritional Sciences, University Park, PA, USA. Electronic address: gcs13@psu.edu.
2
The Pennsylvania State University, Department of Nutritional Sciences, University Park, PA, USA; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, CA, USA.
3
Sanford Research, Sioux Falls, SD, USA.
4
Sanford Research, Sioux Falls, SD, USA; Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
5
Obesity and Metabolism Research Unit, USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA.
6
Obesity and Metabolism Research Unit, USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA; Department of Nutrition, University of California, Davis, CA, USA.

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 4g/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.

KEYWORDS:

DHA; EPA; Epoxides; HDL; LDL; Lipid mediators; Lipoproteins; Metabolic syndrome; Omega-3 acid ethyl esters; Omega-3 fatty acids; Oxylipins; VLDL

PMID:
29413356
DOI:
10.1016/j.plefa.2017.10.006
[Indexed for MEDLINE]

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