Métabolisme et fonctions des acides gras oméga-3 à longue chaîne ...

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Summary Summary N-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, potentially exert beneficial health effects, mainly in cardiovascular diseases, obesity and type 2 diabetes. DHA protects against insulin resistance and obesity in rodents and increases insulin sensitivity in healthy humans. The first objective of our study was to determine the time course of DHA incorporation into phospholipids of different tissues in mice and the effects of DHA supplementation on plasma adiponectin and leptin secretions, two cytokines known to participate in the regulation of insuline sensitivity. We showed an improvement of the secreted adipokine profile in mice fed the DHA-rich diet. This effect was associated with a significant increase in DHA incorporation into phospholipids of all analyzed tissues. The beneficial effects on adipokines were fast, since they were observed as early as 4 days after the initiation of the DHA-rich diet, and long lasting as they were still observed 16 days after the arrest of DHA-rich diet feeding. We also showed an increased adiponectin secretion in mice fed an EPA-rich diet. We then studied the effects of EPA and DHA, and that of their oxygenated derivatives on adiponectin secretion in 3T3-L1 adipocytes. We observed an increased adiponectin secretion after cell enrichment with these n-3 PUFA. Our results suggest that oxygenated metabolites could contribute to this effect. Regarding DHA, we showed a significant increase in adiponectin secretion after cell incubation with protectin DX (PDX). We also showed that only PDX, which has a E,Z,E-conjugated triene motif in his stucture, increased adiponectin secretion, whereas Z,E,E trienes or E,E,E trienes were inactive. Moreover, the triene position in the fatty chain seems to be important for the effect. Regarding EPA, we hypothesized that prostaglandin D 3 (PGD 3 ), an EPA metabolite, may be metabolized to 15-deoxy-delta 12,14 -PGJ 3 19
Summary (15dPGJ 3 ). We synthesized 15dPGJ 3 from a commercial PGD 3 and we verified its structure. We then studied the effects of these two prostaglandins on adiponectin secretion. We observed an increased adiponectin secretion in response to PGD 3 and to 15dPGJ 3 . Overall, these data show that at least part of the vascular protection attributed to longchain omega-3 fatty acids (EPA and DHA) could result from a positive effect on the secretion of adiponectin, an adipocytokine active against insulin-resistance and atherothrombogenesis. Those effects might be due to some specific oxygenated metabolites from both fatty acids. 20
Page 1 and 2: N° d’ordre 2010ISAL0130 année 2
Page 3 and 4: Ce travail a été réalisé au sei
Page 5 and 6: Remerciements Remerciements C’est
Page 7 and 8: Table des matières Table des mati
Page 9 and 10: Table des matières Chapitre 7 - R
Page 11 and 12: Table des matières II.2-2 Effets d
Page 13 and 14: Index des figures et des tableaux F
Page 15 and 16: Index des figures et des tableaux F
Page 17 and 18: Abréviations IBMX 3-isobutyl,1-mé
Page 19: Résumé d’adiponectine alors que
Page 23 and 24: Introduction exerce des propriété
Page 25 and 26: Rappels Bibliographiques Rappels Bi
Page 27 and 28: Rappels Bibliographiques Figure 2:
Page 29 and 30: Rappels Bibliographiques Chapitre 2
Page 31 and 32: Rappels Bibliographiques II.1.1.b)
Page 33 and 34: Rappels Bibliographiques II.1.2 Pro
Page 35 and 36: Rappels Bibliographiques Figure 6:
Page 37 and 38: Rappels Bibliographiques II-2 Les r
Page 39 and 40: Rappels Bibliographiques II.2.2 Les
Page 41 and 42: Rappels Bibliographiques II.2.3 Les
Page 43 and 44: Rappels Bibliographiques des vertè
Page 47 and 48: Rappels Bibliographiques IV.3 La li
Page 49 and 50: Rappels Bibliographiques (DGATs) (C
Page 51 and 52: Rappels Bibliographiques L’insuli
Page 53 and 54: Rappels Bibliographiques Chez l’H
Page 55 and 56: Rappels Bibliographiques V.2 La lep
Page 57 and 58: Rappels Bibliographiques V.3 Le TNF
Page 59 and 60: Rappels Bibliographiques dans le fo
Page 61 and 62: Rappels Bibliographiques d’insuli
Page 65 and 66: Rappels Bibliographiques relativeme
Page 67 and 68: Rappels Bibliographiques VII.3 Modu
Page 69 and 70: Matériels & Méthodes Matériels &
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Matériels & Méthodes I-5 Incubati
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Matériels & Méthodes IV- Mesure d
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Matériels & Méthodes V- Analyse d
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Matériels & Méthodes A B Figure 1
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Matériels & Méthodes Les souris o
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Matériels & Méthodes Figure 15 :
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Résultats Résultats I - Etude in
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Résultats I.2 Incorporation du DHA
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Résultats D Figure 18: Proportions
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Résultats Figure 20: Proportions d
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Résultats Figure 22: Proportions d
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Résultats I.3 Effet d’une alimen
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Résultats L’expression génique
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Résultats A B Figure 27: Concentra
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Résultats comparativement aux sour
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Résultats important dans la régul
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Résultats +20% +50% +77% +95% +80%
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Résultats II.1-2 Effet du DHA et d
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Résultats II.2 Effets de divers tr
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Résultats II.2-2 Effets de molécu
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Résultats II.2-2.b) Géométrie E,
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Résultats II.3 Effets de métaboli
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Résultats , Sig=205,4 Ref =360,100
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Résultats Nous avons ensuite optim
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Résultats Nous avons ensuite suivi
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Résultats La 15dPGJ 3 a été dér
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Résultats II.3-2.b) Comparaison de
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Résultats Concernant le DHA, nos r
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Conclusion générales & Perspectiv
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Conclusion générales & Perspectiv
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Références Bibliographiques Réf
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Références Bibliographiques Bazan
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Références Bibliographiques Cases
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Références Bibliographiques De Vo
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Références Bibliographiques Forma
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Références Bibliographiques Hashi
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Références Bibliographiques Jense
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Références Bibliographiques Krebs
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Références Bibliographiques Lönn
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Références Bibliographiques Monta
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Références Bibliographiques Picku
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Références Bibliographiques Scher
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Références Bibliographiques Soare
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Références Bibliographiques Todor
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Références Bibliographiques Xu J,
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Annexes Annexes 160
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Métabolisme et fonctions des acides gras oméga-3 à longue chaîne ...

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