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Lipidomic profiling and partial least square analysis in LDLR-/- MICE given increasing dose of omega 3 PUFA:F4 -neuroprostanes as a major predictive variable of atherosclerosis regression

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HAL Id: hal-01189968

https://hal.archives-ouvertes.fr/hal-01189968

Submitted on 3 Jun 2020

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Lipidomic profiling and partial least square analysis in LDLR-/- MICE given increasing dose of omega 3 PUFA:F4 -neuroprostanes as a major predictive variable

of atherosclerosis regression

Cécile Gladine, John W Newman, Thierry Durand, Theresa L Pedersen, Jean-Marie Galano, Céline Demougeot, Olivier Berdeaux, Estelle

Pujos-Guillot, André Mazur, Blandine Comte

To cite this version:

Cécile Gladine, John W Newman, Thierry Durand, Theresa L Pedersen, Jean-Marie Galano, et al..

Lipidomic profiling and partial least square analysis in LDLR-/- MICE given increasing dose of omega

3 PUFA:F4 -neuroprostanes as a major predictive variable of atherosclerosis regression. ICTRNH 2013

Second International Congress of Translational Research in Human Nutrition Integrative Approaches

in Nutrition Research, Mar 2013, Clermont-Ferrand, France. 2013. �hal-01189968�

(2)

PO52

Title: L IPIDOMIC PROFILING AND PARTIAL LEAST SQUARE ANALYSIS IN LDLR-/- MICE GIVEN INCREASING DOSE OF OMEGA 3 PUFA: F4-N EUROPROSTANES AS A MAJOR PREDICTIVE VARIABLE OF ATHEROSCLEROSIS REGRESSION

Authors and addresses: Cécile Gladine(1), John W Newman(2,3), Thierry Durand(4), Theresa L Pedersen(2), Jean-Marie Galano(4), Céline Demougeot(5), Olivier Berdeaux(6,7,8), Estelle Pujos- Guillot(1,9), Andrzej Mazur(1), Blandine Comte(1)

(1) INRA, UMR1019, UNH, CRNH Auvergne, Clermont-Ferrand, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France ; (2) Obesity and Metabolism Research Unit, USDA, ARS, Western, Human Nutrition Research Center, Davis, CA, 95616; (3)

Department of Nutrition, University of California, Davis, CA, 95616; (4) Institut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, Universités de Montpellier I et II, France ; (5) EA 4267

Fonctions et Dysfonctions epithéliales, University of Franche Comté, 19 rue Ambroise Paré, 25030 Besançon, France ; (6) CNRS, UMR6265 Centre des Sciences du Goût et de l'Alimentation, Dijon, France ; (7) INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Dijon, France ; (8) Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, Dijon, France ; (9) INRA, UMR 1019, Plateforme d’Exploration du Métabolisme, Clermont-Ferrand, France

Presenting author: Cecile Gladine

Abstract: Objective. Consumption of long chain n-3 PUFA is associated with reduced risk of

cardiovascular disease but the role of their oxygenated metabolites is still unclear. We hypothesized that metabolites issued from the non-enzymatic oxidation of docosahexaenoïc acid (DHA, C22:6 n-3) could play a role in the prevention of atherosclerosis.

Methods and Results. LDLR-/- mice (n=30/group) received for 20 weeks an atherogenic diet (10% lard and 0.045% cholesterol) together with daily oral gavages of a mixture of sunflower and tuna oils providing 0%, 0.1%, 1% and 2% of energy as DHA (Control, DHA1, DHA2 and DHA3 groups respectively). Supplementation with DHA dose-dependently reduced atherosclerotic plaque size (R2=0.97) as well as most cardiovascular risk factors such as plasma triglycerides and cholesterol (R2=0.97 and 0.96 respectively). Targeted lipidomic analyses were used to determine plasma and liver profiles of PUFA and their oxygenated metabolites. As expected, DHA supplementation induced dose-dependent increase of long chain n-3 PUFA (R2=0.95 and 0.99 in plasma and liver respectively) but was also associated with an increased production of n-3 PUFA’s oxylipins and F4-Neuroprostanes, a major peroxidation metabolite of DHA. Finally, correlation, hierarchical cluster and partial least square analysis of the overall dataset revealed that the liver content of F4-Neuroprostanes was both the variable the most negatively correlated with plaque progression and one of the two major predictive variables of plaque regression.

Conclusion. This study shows the antiatherogenic effect of DHA could in part be achieved by one of its major peroxidation metabolites, the F4-Neuroprostanes.

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