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Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects.

Newman JW, Pedersen TL, Brandenburg VR, Harris WS, Shearer GC - PLoS ONE (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

Trial registration: ClinicalTrials.gov NCT00959842.

No MeSH data available.


Related in: MedlinePlus

Correlation Heat Map for HDL and LDL.The Pearson correlation coefficient (r) among lipoprotein-oxylipins for HDL (A) and LDL (B) is shown before treatment (top), after treatment (middle) as correlation of nM oxylipin/mM PL along with the change in oxylipins due to treatment (bottom) expressed as ln(nM oxylipinfinal/mM PLfinal)/ln(nM oxylipinbaseline/mM PLbaseline).
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pone-0111471-g004: Correlation Heat Map for HDL and LDL.The Pearson correlation coefficient (r) among lipoprotein-oxylipins for HDL (A) and LDL (B) is shown before treatment (top), after treatment (middle) as correlation of nM oxylipin/mM PL along with the change in oxylipins due to treatment (bottom) expressed as ln(nM oxylipinfinal/mM PLfinal)/ln(nM oxylipinbaseline/mM PLbaseline).

Mentions: The Pearson correlation matrices before and after P-OM3 treatment are presented in Figures 4 and 5. These matrices are useful in describing the independence of oxylipins species. At their baseline visit, the median /inter-quartile range/ correlation among plasma oxylipins was 0.59 /0.39, 0.72/, a relatively strong interdependence of oxylipins, irrespective of parent FA or chemistry class. HDL and LDL oxylipins (Figure 4) were more independent; LDL oxylipins were the most independent (r = 0.32 /0.09, 0.55/), with nearly as much independence among HDL oxylipins, 0.44 /0.25, 0.59/. VLDL were the most interdependent, with strong correlations (r = 0.85 /0.77, 0.91/ among nearly every oxylipin (Figure 5). P-OM3 treatment disrupted these interdependencies, demonstrated also by a shift in the distribution of correlation coefficients (Figure S3 in File S1). The effect was most pronounced among VLDL oxylipins, in which the correlations dropped by 0.52 to 0.33 /0.11, 0.66/, meaning oxylipins were less dependent one another and therefore reflective of more than one latent factor. In a similar manner, the median correlation also dropped among HDL and plasma oxylipins, to 020 /−0.03, 0.49/ and 0.34 /0.11, 0.61/ respectively, but dropped more moderately in LDL, by 0.08 to 0.24 /0.01, 0.49/.


Effect of omega-3 fatty acid ethyl esters on the oxylipin composition of lipoproteins in hypertriglyceridemic, statin-treated subjects.

Newman JW, Pedersen TL, Brandenburg VR, Harris WS, Shearer GC - PLoS ONE (2014)

Correlation Heat Map for HDL and LDL.The Pearson correlation coefficient (r) among lipoprotein-oxylipins for HDL (A) and LDL (B) is shown before treatment (top), after treatment (middle) as correlation of nM oxylipin/mM PL along with the change in oxylipins due to treatment (bottom) expressed as ln(nM oxylipinfinal/mM PLfinal)/ln(nM oxylipinbaseline/mM PLbaseline).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230929&req=5

pone-0111471-g004: Correlation Heat Map for HDL and LDL.The Pearson correlation coefficient (r) among lipoprotein-oxylipins for HDL (A) and LDL (B) is shown before treatment (top), after treatment (middle) as correlation of nM oxylipin/mM PL along with the change in oxylipins due to treatment (bottom) expressed as ln(nM oxylipinfinal/mM PLfinal)/ln(nM oxylipinbaseline/mM PLbaseline).
Mentions: The Pearson correlation matrices before and after P-OM3 treatment are presented in Figures 4 and 5. These matrices are useful in describing the independence of oxylipins species. At their baseline visit, the median /inter-quartile range/ correlation among plasma oxylipins was 0.59 /0.39, 0.72/, a relatively strong interdependence of oxylipins, irrespective of parent FA or chemistry class. HDL and LDL oxylipins (Figure 4) were more independent; LDL oxylipins were the most independent (r = 0.32 /0.09, 0.55/), with nearly as much independence among HDL oxylipins, 0.44 /0.25, 0.59/. VLDL were the most interdependent, with strong correlations (r = 0.85 /0.77, 0.91/ among nearly every oxylipin (Figure 5). P-OM3 treatment disrupted these interdependencies, demonstrated also by a shift in the distribution of correlation coefficients (Figure S3 in File S1). The effect was most pronounced among VLDL oxylipins, in which the correlations dropped by 0.52 to 0.33 /0.11, 0.66/, meaning oxylipins were less dependent one another and therefore reflective of more than one latent factor. In a similar manner, the median correlation also dropped among HDL and plasma oxylipins, to 020 /−0.03, 0.49/ and 0.34 /0.11, 0.61/ respectively, but dropped more moderately in LDL, by 0.08 to 0.24 /0.01, 0.49/.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

Trial registration: ClinicalTrials.gov NCT00959842.

No MeSH data available.


Related in: MedlinePlus