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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 fatty acids epoxides and vicinal diols.The per-phospholipid concentrations of epoxides as AA-derived EpETrEs (A), EPA-derived EpETEs (B), DHA-derived EpDPEs (B) AA-derived DiHETrEs (C), EPA-derived Di HETEs (D), and DHA-derived DiHDPAs (D) are shown in lipoproteins and plasma. Regioisomers are color coded by our best estimate of homologous double-bond positions across all figures. Epoxides are products of CYP-epoxygenase and can also be generated via autooxidation. Vicinal diols are the unique products of soluble epoxide hydrolase on epoxides. The effect of P-OM3 adjusted for age and sex was uniform regardless of regioisomer. The mean adjusted effects are shown graphically in Figure S2 in File S1; A mixed model ANOVA was used to test for differences on ln[nM oxylipin/mM PL]. The least-squares mean [95% CI] are shown. Tukey's HSD test was used for post hoc differences between regioisomer levels, and regioisomers sharing a letter are not different. Since no interactions were significant, the term was dropped and the parameter estimate was used to calculate a mean effect [95% CI]. Note that since the test was on log-transformed data, the effect is a proportional one (i.e. percent change). Note the log scale of the y-axis. Note that EPA and DHA oxylipins are shown on the same graph for brevity, but constitute separate ANOVA tests.
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pone-0111471-g003: Distribution of fatty acids epoxides and vicinal diols.The per-phospholipid concentrations of epoxides as AA-derived EpETrEs (A), EPA-derived EpETEs (B), DHA-derived EpDPEs (B) AA-derived DiHETrEs (C), EPA-derived Di HETEs (D), and DHA-derived DiHDPAs (D) are shown in lipoproteins and plasma. Regioisomers are color coded by our best estimate of homologous double-bond positions across all figures. Epoxides are products of CYP-epoxygenase and can also be generated via autooxidation. Vicinal diols are the unique products of soluble epoxide hydrolase on epoxides. The effect of P-OM3 adjusted for age and sex was uniform regardless of regioisomer. The mean adjusted effects are shown graphically in Figure S2 in File S1; A mixed model ANOVA was used to test for differences on ln[nM oxylipin/mM PL]. The least-squares mean [95% CI] are shown. Tukey's HSD test was used for post hoc differences between regioisomer levels, and regioisomers sharing a letter are not different. Since no interactions were significant, the term was dropped and the parameter estimate was used to calculate a mean effect [95% CI]. Note that since the test was on log-transformed data, the effect is a proportional one (i.e. percent change). Note the log scale of the y-axis. Note that EPA and DHA oxylipins are shown on the same graph for brevity, but constitute separate ANOVA tests.

Mentions: Fatty acid epoxides are produced by CYP-epoxygenases, but can also be autooxidatively generated. With the exception of the 5(6)-EpETrE, they are hydrolyzed by soluble epoxide hydrolase to produce vicinal diols. Epoxides were present at much higher levels than diols and were most abundant in HDL followed by LDL and VLDL. 14(15)- and 11(12)-EpETrE were the most abundant epoxides followed by the 8(9)-EpETrE (Figure 3). The DHA-derived 16(17)-EpDPE was the next most abundant, followed by EPA-epoxides. Among vicinal diols, the most abundant AA-diol was the 5,6-DiHETrE, decreasing in abundance with progression toward the ω-terminus, in reverse order as epoxide abundances. EPA diols were as, or more, abundant as AA-diols in many cases; the DHA-diol 19,20-DiHDPA was the least abundant.


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 fatty acids epoxides and vicinal diols.The per-phospholipid concentrations of epoxides as AA-derived EpETrEs (A), EPA-derived EpETEs (B), DHA-derived EpDPEs (B) AA-derived DiHETrEs (C), EPA-derived Di HETEs (D), and DHA-derived DiHDPAs (D) are shown in lipoproteins and plasma. Regioisomers are color coded by our best estimate of homologous double-bond positions across all figures. Epoxides are products of CYP-epoxygenase and can also be generated via autooxidation. Vicinal diols are the unique products of soluble epoxide hydrolase on epoxides. The effect of P-OM3 adjusted for age and sex was uniform regardless of regioisomer. The mean adjusted effects are shown graphically in Figure S2 in File S1; A mixed model ANOVA was used to test for differences on ln[nM oxylipin/mM PL]. The least-squares mean [95% CI] are shown. Tukey's HSD test was used for post hoc differences between regioisomer levels, and regioisomers sharing a letter are not different. Since no interactions were significant, the term was dropped and the parameter estimate was used to calculate a mean effect [95% CI]. Note that since the test was on log-transformed data, the effect is a proportional one (i.e. percent change). Note the log scale of the y-axis. Note that EPA and DHA oxylipins are shown on the same graph for brevity, but constitute separate ANOVA tests.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230929&req=5

pone-0111471-g003: Distribution of fatty acids epoxides and vicinal diols.The per-phospholipid concentrations of epoxides as AA-derived EpETrEs (A), EPA-derived EpETEs (B), DHA-derived EpDPEs (B) AA-derived DiHETrEs (C), EPA-derived Di HETEs (D), and DHA-derived DiHDPAs (D) are shown in lipoproteins and plasma. Regioisomers are color coded by our best estimate of homologous double-bond positions across all figures. Epoxides are products of CYP-epoxygenase and can also be generated via autooxidation. Vicinal diols are the unique products of soluble epoxide hydrolase on epoxides. The effect of P-OM3 adjusted for age and sex was uniform regardless of regioisomer. The mean adjusted effects are shown graphically in Figure S2 in File S1; A mixed model ANOVA was used to test for differences on ln[nM oxylipin/mM PL]. The least-squares mean [95% CI] are shown. Tukey's HSD test was used for post hoc differences between regioisomer levels, and regioisomers sharing a letter are not different. Since no interactions were significant, the term was dropped and the parameter estimate was used to calculate a mean effect [95% CI]. Note that since the test was on log-transformed data, the effect is a proportional one (i.e. percent change). Note the log scale of the y-axis. Note that EPA and DHA oxylipins are shown on the same graph for brevity, but constitute separate ANOVA tests.
Mentions: Fatty acid epoxides are produced by CYP-epoxygenases, but can also be autooxidatively generated. With the exception of the 5(6)-EpETrE, they are hydrolyzed by soluble epoxide hydrolase to produce vicinal diols. Epoxides were present at much higher levels than diols and were most abundant in HDL followed by LDL and VLDL. 14(15)- and 11(12)-EpETrE were the most abundant epoxides followed by the 8(9)-EpETrE (Figure 3). The DHA-derived 16(17)-EpDPE was the next most abundant, followed by EPA-epoxides. Among vicinal diols, the most abundant AA-diol was the 5,6-DiHETrE, decreasing in abundance with progression toward the ω-terminus, in reverse order as epoxide abundances. EPA diols were as, or more, abundant as AA-diols in many cases; the DHA-diol 19,20-DiHDPA was the least abundant.

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