Caractérisation d'un modèle de dysfonction endothéliale postprandiale chez le rat sain : Intérêt de la modulation de la nature des protéines en termes de prévention du risque cardiovasculaire

The alteration in vascular endothelial function is the key event in the pathophysiology of atherosclerosis. In healthy humans, a single high-saturated fat/high sucrose meal induces a series of transient vascular, inflammatory and oxidative disturbances that constitute a complex proatherogenic phenotype. However, little is known on early pathways that occur during the postprandial state. Furthermore, some amino acids have been suspected of having an impact on vascular homeostasis, but there is a paucity of information regarding the effect of dietary protein on the initiation of endothelial dysfunction. We aimed to characterize an animal model of postprandial endothelial dysfunction induced by a high-saturated fat meal (HFM), in healthy rats, in which to delineate the early inflammatory response in adipose tissue, and examine whether the nitric oxide (NO) pathway is impaired in the postprandial setting. Using this model, we have explored whether rapeseed protein, an emergent protein rich in arginine and cysteine may modulate postprandial endothelial dysfunction. We have clearly characterized a rat model of postprandial endothelial dysfunction, featuring oxidative stress, impairment of the NO pathway and low-grade inflammation. We have revealed that inflammatory pathways are activated very early in the visceral adipose tissue, and the HFM markedly impair basal systemic whole-body NO production. Interestingly, modulating the protein source of the HFM has a marked protective effect on postprandial endothelial function in healthy rats. Substituting rapeseed protein for milk protein in an HFM totally suppresses postprandial impairment of vascular reactivity and partially decreases postprandial oxidative stress. These results urge on further studies to examine the clinical relevance of specific protein source, in dietary strategies for the prevention of cardiovascular diseases.L'altération de la fonction endothéliale vasculaire est un phénomène précoce et central dans la pathogenèse de l'athérosclérose. Chez l'homme sain, un repas trop gras et trop sucré induit un ensemble de désordres vasculaires postprandiaux dont les voies de signalisation restent encore méconnues. Par ailleurs, si certains acides aminés participent à l'homéostasie vasculaire, aucune étude n'a examiné les effets d'une modulation de la nature des protéines d'un repas sur les fonctions endothéliales vasculaires. Afin de préciser l'implication des voies de signalisation du monoxyde d'azote (NO), molécule clé dans l'homéostasie vasculaire, et d'étudier les composantes de la réponse inflammatoire postprandiale, nous avons cherché à caractériser, chez le rat sain, les principaux paramètres de la dysfonction endothéliale induite par un repas riche en acides gras saturés et en saccharose. Nous avons ensuite examiné le potentiel des protéines de colza, naturellement riche en arginine et en cystéine, précurseurs respectifs du NO et du glutathion, à moduler la dysfonction endothéliale postprandiale. De ce travail de thèse s'est dégagé un solide modèle animal de dysfonction endothéliale postprandiale caractérisée par une diminution de la réactivité vasculaire NO-dépendante, une inflammation à bas bruit et du stress oxydant. Ces évènements postprandiaux délétères étaient associés à une diminution de la production corps-entier du NO et une activation de NF-κB au niveau du tissu adipeux viscéral. Enfin, nous avons montré que les protéines de colza, à des doses nutritionnelles, réduisait le stress oxydant, et prévenait complètement l'altération de la réactivité vasculaire NO-dépendante induits par l'ingestion d'un repas hyperlipidique. Cet effet protecteur des protéines de colza, nous invite à envisager, chez l'homme, la modulation de la nature des protéines d'un repas comme une véritable approche nutritionnelle de prévention du risque cardiovasculaire

Early postprandial low-grade inflammation after high-fat meal in healthy rats : possible involvement of visceral adipose tissue

International audienceIn the postprandial period, low-grade inflammation may contribute to vascular endothelial dysfunction, a hallmark of atherogenesis. Little is known about the involvement of the adipose tissue in the initiation of the postprandial inflammatory response such as obtained after a high-saturated fat meal (HFM). In the present study, we first studied the time course of appearance of systemic inflammation after a HFM in healthy rats, and then we investigated whether a HFM activates the inflammatory signaling in the visceral adipose tissue, with a focus on the key component, nuclear factor-kappaB (NF-kappaB). Two hours after the HFM, plasma IL-6 and PAI-1, but not plasma C-reactive protein and soluble intracellular adhesion molecule-1, showed a marked, transient increase. These changes were specific to the postprandial state as not observed after a control water load. Neutrophils count and activation markers CD11B and CD62L, assessed by flow cytometry, also rose significantly 2 h after the HFM, while remaining steady after the control. At the same time, the HFM decreased significantly B-cell count and expression of the activation marker CD62L. Interestingly, at the same early time after the HFM, in the visceral adipose tissue, there was a 2.2-fold increase in the activation of NF-kappaB (p65) in nuclear extract and an increase in IL-6 mRNA. As far as we know, this is the first study evidencing an acute, postprandial activation of inflammation in visceral adipose tissue. This early activation of NF-kappaB pathway after a HFM may play a triggering role in the initiation of the complex postprandial proatherogenic phenotype

Whole-body basal nitric oxide production is impaired in postprandial endothelial dysfunction in healthy rats

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Rapeseed Protein in a High-Fat Mixed Meal Alleviates Postprandial Systemic and Vascular Oxidative Stress and Prevents Vascular Endothelial Dysfunction in Healthy Rats

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