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Lipid profiling following intake of the omega 3 fatty acid DHA identifies the peroxidized metabolites F4-neuroprostanes as the best predictors of atherosclerosis prevention.

Gladine C, Newman JW, Durand T, Pedersen TL, Galano JM, Demougeot C, Berdeaux O, Pujos-Guillot E, Mazur A, Comte B - PLoS ONE (2014)

Bottom Line: A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation.Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level.While these may contribute to the anti-atherogenic effects of DHA, further in vitro investigations are needed to confirm such a contention and to decipher the molecular mechanisms of action.

View Article: PubMed Central - PubMed

Affiliation: UMR1019 Unité de Nutrition Humaine (UNH), INRA, CRNH Auvergne, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.

ABSTRACT
The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediator profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to atherosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR(-/-)) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose-dependent reduction of atherosclerosis (R(2) = 0.97, p = 0.02), triglyceridemia (R(2) = 0.97, p = 0.01) and cholesterolemia (R(2) = 0.96, p<0.01). Targeted lipidomic analyses revealed that both the profiles of EPA and DHA and their corresponding oxygenated metabolites were substantially modulated in plasma and liver. Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable most negatively correlated with the plaque extent (p<0.001) and along with plasma EPA-derived diols was an important mathematical positive predictor of atherosclerosis prevention. Thus, oxygenated n-3 PUFAs, and F4-neuroprostanes in particular, are potential biomarkers of DHA-associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA, further in vitro investigations are needed to confirm such a contention and to decipher the molecular mechanisms of action.

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Correlations between the doses of DHA and the cardiovascular parameters (i.e. plasma TG and TC, liver TG and TC, sBP, and plaque area).LDLR−/− mice were given by daily oral gavages (20 weeks) either oleic acid rich sunflower oil (Control group) or a mixture of oleic acid rich sunflower oil and DHA rich tuna oil providing 0.1%, 1% or 2% of energy as DHA (DHA1, DHA2, and DHA3 groups respectively).
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pone-0089393-g001: Correlations between the doses of DHA and the cardiovascular parameters (i.e. plasma TG and TC, liver TG and TC, sBP, and plaque area).LDLR−/− mice were given by daily oral gavages (20 weeks) either oleic acid rich sunflower oil (Control group) or a mixture of oleic acid rich sunflower oil and DHA rich tuna oil providing 0.1%, 1% or 2% of energy as DHA (DHA1, DHA2, and DHA3 groups respectively).

Mentions: The dose-response effects of DHA supplementation were evaluated on several cardiovascular risk factors (i.e. plasma and hepatic lipids, sBP) and atherosclerosis as shown in Figure 1. The doses of DHA given to the LDLR−/− mice (0, 0.1, 1 and 2% of energy as DHA) were negatively correlated with plasma TG and TC (R2 = 0.97, p = 0.01 and R2 = 0.96, p<0.01 respectively) as well as with liver contents of TG and TC (R2 = 0.89, p = 0.06 and R2 = 0.93, p = 0.03) (Figure 1A). There was also a strong negative correlation with atherosclerotic plaque area (R2 = 0.97, p = 0.02; Figure 1B). With sBP, the correlation did not reach significance (R2 = 0.84, p = 0.08; Figure 1B). The effects of DHA on cardiovascular risk parameters and atherosclerosis were especially strong in the DHA3 group (Table S4 in File S1) in which plasma levels of TG and TC were reduced (p<0.05) by 37 and 28% respectively, while liver concentrations of TG and TC were decreased (p<0.05) by 56 and 47% respectively. Concerning atherosclerotic plaque extent (Figure 2) and sBP (Table S5 in File S1), the reductions induced by DHA supplementation were also especially pronounced in the DHA3 group (−35 and −16%, p<0.05 respectively).


Lipid profiling following intake of the omega 3 fatty acid DHA identifies the peroxidized metabolites F4-neuroprostanes as the best predictors of atherosclerosis prevention.

Gladine C, Newman JW, Durand T, Pedersen TL, Galano JM, Demougeot C, Berdeaux O, Pujos-Guillot E, Mazur A, Comte B - PLoS ONE (2014)

Correlations between the doses of DHA and the cardiovascular parameters (i.e. plasma TG and TC, liver TG and TC, sBP, and plaque area).LDLR−/− mice were given by daily oral gavages (20 weeks) either oleic acid rich sunflower oil (Control group) or a mixture of oleic acid rich sunflower oil and DHA rich tuna oil providing 0.1%, 1% or 2% of energy as DHA (DHA1, DHA2, and DHA3 groups respectively).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3928438&req=5

pone-0089393-g001: Correlations between the doses of DHA and the cardiovascular parameters (i.e. plasma TG and TC, liver TG and TC, sBP, and plaque area).LDLR−/− mice were given by daily oral gavages (20 weeks) either oleic acid rich sunflower oil (Control group) or a mixture of oleic acid rich sunflower oil and DHA rich tuna oil providing 0.1%, 1% or 2% of energy as DHA (DHA1, DHA2, and DHA3 groups respectively).
Mentions: The dose-response effects of DHA supplementation were evaluated on several cardiovascular risk factors (i.e. plasma and hepatic lipids, sBP) and atherosclerosis as shown in Figure 1. The doses of DHA given to the LDLR−/− mice (0, 0.1, 1 and 2% of energy as DHA) were negatively correlated with plasma TG and TC (R2 = 0.97, p = 0.01 and R2 = 0.96, p<0.01 respectively) as well as with liver contents of TG and TC (R2 = 0.89, p = 0.06 and R2 = 0.93, p = 0.03) (Figure 1A). There was also a strong negative correlation with atherosclerotic plaque area (R2 = 0.97, p = 0.02; Figure 1B). With sBP, the correlation did not reach significance (R2 = 0.84, p = 0.08; Figure 1B). The effects of DHA on cardiovascular risk parameters and atherosclerosis were especially strong in the DHA3 group (Table S4 in File S1) in which plasma levels of TG and TC were reduced (p<0.05) by 37 and 28% respectively, while liver concentrations of TG and TC were decreased (p<0.05) by 56 and 47% respectively. Concerning atherosclerotic plaque extent (Figure 2) and sBP (Table S5 in File S1), the reductions induced by DHA supplementation were also especially pronounced in the DHA3 group (−35 and −16%, p<0.05 respectively).

Bottom Line: A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation.Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level.While these may contribute to the anti-atherogenic effects of DHA, further in vitro investigations are needed to confirm such a contention and to decipher the molecular mechanisms of action.

View Article: PubMed Central - PubMed

Affiliation: UMR1019 Unité de Nutrition Humaine (UNH), INRA, CRNH Auvergne, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.

ABSTRACT
The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediator profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to atherosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR(-/-)) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose-dependent reduction of atherosclerosis (R(2) = 0.97, p = 0.02), triglyceridemia (R(2) = 0.97, p = 0.01) and cholesterolemia (R(2) = 0.96, p<0.01). Targeted lipidomic analyses revealed that both the profiles of EPA and DHA and their corresponding oxygenated metabolites were substantially modulated in plasma and liver. Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable most negatively correlated with the plaque extent (p<0.001) and along with plasma EPA-derived diols was an important mathematical positive predictor of atherosclerosis prevention. Thus, oxygenated n-3 PUFAs, and F4-neuroprostanes in particular, are potential biomarkers of DHA-associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA, further in vitro investigations are needed to confirm such a contention and to decipher the molecular mechanisms of action.

Show MeSH
Related in: MedlinePlus