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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 acid alcohols and ketones.The per-phospholipid concentration of mid-chain alcohols as AA-derived HETEs (A), EPA-derived HEPEs (B), DHA-derived HDoHEs (B) and AA-derived ketones (C) are shown in lipoproteins and plasma. Regioisomers are shaped and shaded by our best estimate of homologous double-bond positions across all figures. HETEs are mainly products of LOX, but are also products of CYP and autooxidation. KETEs are the HETE-dehydrogenase product of HETEs. Values for EPA and DHA ketones were not available. 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 difference [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 graphs for brevity, but constitute separate ANOVA tests. a9-HETE is an autooxidative product and is not formed by LOX.
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pone-0111471-g002: Distribution of fatty acid alcohols and ketones.The per-phospholipid concentration of mid-chain alcohols as AA-derived HETEs (A), EPA-derived HEPEs (B), DHA-derived HDoHEs (B) and AA-derived ketones (C) are shown in lipoproteins and plasma. Regioisomers are shaped and shaded by our best estimate of homologous double-bond positions across all figures. HETEs are mainly products of LOX, but are also products of CYP and autooxidation. KETEs are the HETE-dehydrogenase product of HETEs. Values for EPA and DHA ketones were not available. 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 difference [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 graphs for brevity, but constitute separate ANOVA tests. a9-HETE is an autooxidative product and is not formed by LOX.

Mentions: The per-phospholipid concentration (nM oxylipin/mM PL) of AA, EPA and DHA mid-chain alcohols (HETEs, HEPEs, and HDoHEs respectively) at the baseline and final visits in HDL, LDL and VLDL are represented in Figure 2 and compared to plasma. P-OM3 did not affect the abundance of the regioisomers relative to each other (e.g. 5-HEPE to 15-HEPE). As previously reported [8], 15-HETE and 5-HETE were most abundant in plasma, but in lipoproteins 5-HETE was about as abundant as 9-HETE, an oxylipin that is not produced enzymatically and thought to be strictly an autooxidation product [19]. HDL contained the most HETEs per mole phospholipid and appears to represent the largest HETE pool in plasma. Among omega-3 alcohols, the DHA-derived 17-HDoHE was nearly as abundant as some HETEs in HDL and VLDL, but not in LDL. EPA- and DHA-alcohols both reflected the trend seen with HETEs, being most abundant in HDL followed by LDL then VLDL.


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 acid alcohols and ketones.The per-phospholipid concentration of mid-chain alcohols as AA-derived HETEs (A), EPA-derived HEPEs (B), DHA-derived HDoHEs (B) and AA-derived ketones (C) are shown in lipoproteins and plasma. Regioisomers are shaped and shaded by our best estimate of homologous double-bond positions across all figures. HETEs are mainly products of LOX, but are also products of CYP and autooxidation. KETEs are the HETE-dehydrogenase product of HETEs. Values for EPA and DHA ketones were not available. 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 difference [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 graphs for brevity, but constitute separate ANOVA tests. a9-HETE is an autooxidative product and is not formed by LOX.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230929&req=5

pone-0111471-g002: Distribution of fatty acid alcohols and ketones.The per-phospholipid concentration of mid-chain alcohols as AA-derived HETEs (A), EPA-derived HEPEs (B), DHA-derived HDoHEs (B) and AA-derived ketones (C) are shown in lipoproteins and plasma. Regioisomers are shaped and shaded by our best estimate of homologous double-bond positions across all figures. HETEs are mainly products of LOX, but are also products of CYP and autooxidation. KETEs are the HETE-dehydrogenase product of HETEs. Values for EPA and DHA ketones were not available. 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 difference [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 graphs for brevity, but constitute separate ANOVA tests. a9-HETE is an autooxidative product and is not formed by LOX.
Mentions: The per-phospholipid concentration (nM oxylipin/mM PL) of AA, EPA and DHA mid-chain alcohols (HETEs, HEPEs, and HDoHEs respectively) at the baseline and final visits in HDL, LDL and VLDL are represented in Figure 2 and compared to plasma. P-OM3 did not affect the abundance of the regioisomers relative to each other (e.g. 5-HEPE to 15-HEPE). As previously reported [8], 15-HETE and 5-HETE were most abundant in plasma, but in lipoproteins 5-HETE was about as abundant as 9-HETE, an oxylipin that is not produced enzymatically and thought to be strictly an autooxidation product [19]. HDL contained the most HETEs per mole phospholipid and appears to represent the largest HETE pool in plasma. Among omega-3 alcohols, the DHA-derived 17-HDoHE was nearly as abundant as some HETEs in HDL and VLDL, but not in LDL. EPA- and DHA-alcohols both reflected the trend seen with HETEs, being most abundant in HDL followed by LDL then VLDL.

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