Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects.
BACKGROUND
Oxylipins mediate inflammation, vascular tension, and more. Their presence in lipoproteins could explain why lipoproteins mediate nearly identical activities.


METHODS
To determine how oxylipins are distributed in the lipoproteins of hypertriglyceridemic subjects, and whether omega-3 fatty acids alter them in a manner consistent with improved cardiovascular health, we recruited 15 dyslipidemic subjects whose levels of low density lipoprotein cholesterol (LDL-C) were at goal but who remained hypertriglyceridemic (200-499 mg/dL). They were treated them with the indicated dose of 4 g/d omega-3 acid ethyl esters (P-OM3) for 8 weeks. Measured oxylipins included mid-chain alcohols (HETEs, HEPEs and HDoHEs), ketones (KETEs), epoxides (as EpETrEs, EpETEs, and EpDPEs).


RESULTS
At baseline, arachidonate-oxylipins (HETEs, KETEs, and EpETrEs) were most abundant in plasma with the greatest fraction of total abundance (mean |95% CI|) being carried in high density lipoproteins (HDL); 42% |31, 57| followed by very low density lipoproteins (VLDL); 27% |20, 36|; and LDL 21% |16, 28|. EPA- and DHA-derived oxylipins constituted less than 11% of total. HDL carried alcohols and epoxides but VLDL was also rich in ketones. Treatment decreased AA-derived oxylipins across lipoprotein classes (-23% |-33, -12|, p = 0.0003), and expanded EPA-(322% |241, 422|, p<0.0001) and DHA-derived oxylipins (123% |80, 176|, p<0.0001).


CONCLUSIONS
Each lipoprotein class carries a unique oxylipin complement. P-OM3 treatment alters the oxylipin content of all classes, reducing pro-inflammatory and increasing anti-inflammatory species, consistent with the improved inflammatory and vascular status associated with the treatment.


BACKGROUND
ClinicalTrials.gov NCT00959842.
USDA, ARS, WHNRC, Obesity and Metabolism Research Unit, Davis, CA, United States of America; Department of Nutrition, University of California Davis, Davis, CA, United States of America.
John W
JW
Newman
USDA, ARS, WHNRC, Obesity and Metabolism Research Unit, Davis, CA, United States of America.
Theresa L
TL
Pedersen
Family Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America.
Verdayne R
VR
Brandenburg
Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America.
William S
WS
Harris
Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America; Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America; Cardiovascular Health Research Center, Sanford Research/USD, Sioux Falls, South Dakota, United States of America; Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Gregory C
GC
Shearer
D016718:Arachidonic Acid / Q000097:blood; D004852:Epoxy Compounds / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007659:Ketones / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D054883:Oxylipins / Q000097:blood* / Q000378:metabolism
D004852:Epoxy Compounds; D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007659:Ketones; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D054883:Oxylipins; D016718:Arachidonic Acid