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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

Distribution of oxylipins in plasma compartments.The distributions of oxylipins are expressed as a percent of the total baseline abundance before and after treatment. A: Oxylipins in plasma by parent fatty acid and chemistry, regardless of distribution in HDL, LDL, VLDL, or ‘free’. A mixed-model ANOVA was used for each FA. B: Oxylipins in lipoprotein by parent fatty acid, regardless of chemistry. A mixed-model ANOVA was used for each FA pool. n = 14: LDL was not recovered for one subject, making total calculations impossible. *p<0.05, **p<0.0005 versus baseline. Letters (A,B,C) indicate results of Tukey's HSD test for differences between lipoproteins. Those sharing a letter are not different.
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pone-0111471-g001: Distribution of oxylipins in plasma compartments.The distributions of oxylipins are expressed as a percent of the total baseline abundance before and after treatment. A: Oxylipins in plasma by parent fatty acid and chemistry, regardless of distribution in HDL, LDL, VLDL, or ‘free’. A mixed-model ANOVA was used for each FA. B: Oxylipins in lipoprotein by parent fatty acid, regardless of chemistry. A mixed-model ANOVA was used for each FA pool. n = 14: LDL was not recovered for one subject, making total calculations impossible. *p<0.05, **p<0.0005 versus baseline. Letters (A,B,C) indicate results of Tukey's HSD test for differences between lipoproteins. Those sharing a letter are not different.

Mentions: Plasma oxylipins at baseline were primarily represented by AA-alcohols (HETEs), secondly by AA-ketones (KETEs), thirdly by AA-epoxides (EpETrEs), and then by EPA- and DHA-oxylipins (Figure 1). Since the change in AA-alcohols, AA-Ketones, and AA-epoxides was the same (pinteraction = 0.93), the pooled estimate for reduction in AA-oxylipins was −23% /−33, −12/, p = 0.0003. Vicinal diols and other AA-oxylipins (not visible) followed the same trend however we did not formally test them since their lower abundance meant different variance. EPA pools were likewise uniformly expanded by 322% /241, 422/, p<0.0001, and DHA pools by 123% /80, 176/, p<0.0001; (EPA pinteraction = 0.70 and DHA pinteraction = 0.71). Treatment with P-OM3 reduced both the total and proportional abundance of AA-oxylipins, and increased the amount of EPA- and DHA-oxylipins.


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)

Distribution of oxylipins in plasma compartments.The distributions of oxylipins are expressed as a percent of the total baseline abundance before and after treatment. A: Oxylipins in plasma by parent fatty acid and chemistry, regardless of distribution in HDL, LDL, VLDL, or ‘free’. A mixed-model ANOVA was used for each FA. B: Oxylipins in lipoprotein by parent fatty acid, regardless of chemistry. A mixed-model ANOVA was used for each FA pool. n = 14: LDL was not recovered for one subject, making total calculations impossible. *p<0.05, **p<0.0005 versus baseline. Letters (A,B,C) indicate results of Tukey's HSD test for differences between lipoproteins. Those sharing a letter are not different.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230929&req=5

pone-0111471-g001: Distribution of oxylipins in plasma compartments.The distributions of oxylipins are expressed as a percent of the total baseline abundance before and after treatment. A: Oxylipins in plasma by parent fatty acid and chemistry, regardless of distribution in HDL, LDL, VLDL, or ‘free’. A mixed-model ANOVA was used for each FA. B: Oxylipins in lipoprotein by parent fatty acid, regardless of chemistry. A mixed-model ANOVA was used for each FA pool. n = 14: LDL was not recovered for one subject, making total calculations impossible. *p<0.05, **p<0.0005 versus baseline. Letters (A,B,C) indicate results of Tukey's HSD test for differences between lipoproteins. Those sharing a letter are not different.
Mentions: Plasma oxylipins at baseline were primarily represented by AA-alcohols (HETEs), secondly by AA-ketones (KETEs), thirdly by AA-epoxides (EpETrEs), and then by EPA- and DHA-oxylipins (Figure 1). Since the change in AA-alcohols, AA-Ketones, and AA-epoxides was the same (pinteraction = 0.93), the pooled estimate for reduction in AA-oxylipins was −23% /−33, −12/, p = 0.0003. Vicinal diols and other AA-oxylipins (not visible) followed the same trend however we did not formally test them since their lower abundance meant different variance. EPA pools were likewise uniformly expanded by 322% /241, 422/, p<0.0001, and DHA pools by 123% /80, 176/, p<0.0001; (EPA pinteraction = 0.70 and DHA pinteraction = 0.71). Treatment with P-OM3 reduced both the total and proportional abundance of AA-oxylipins, and increased the amount of EPA- and DHA-oxylipins.

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