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Prebiotics supplementation improves the endothelial dysfunction in n-3 PUFA-depleted ApoE-/-mice

  • Emilie Catry1,
  • Géraldine Rath2,
  • Barbara D Pachikian1,
  • Audrey M Neyrinck1,
  • Patrice D Cani1,
  • Chantal Dessy2 and
  • Nathalie M Delzenne1Email author
Archives of Public HealthThe official journal of the Belgian Public Health Association201472(Suppl 1):O5

Published: 6 June 2014


Our previous studies demonstrated that dietary n-3 polyunsaturated fatty acids (PUFA) deficiency promotes the development of non-alcoholic fatty liver disease in mice, and that modification of gut microbiota composition by prebiotics (non-digestible fructans) can improve the hepatic steatosis and serum lipids in this model [1, 2]. The present study has been designed to analyze the potential involvement of prebiotic supplementation on endothelial dysfunction in n-3 PUFA-depleted ApoE knock-out mice.

Material and methods

Wild-type (WT, n=6) and ApoE-/- (KO, n=6) mice were fed with a n-3 PUFA-depleted diet for 12 weeks. Fifteen days before the end, WT (n=3) and KO (n=3) mice were supplemented with fructans as prebiotics (PRE). Second and third generation mesenteric arteries were isolated and mounted on a wire myograph. After normalization, arteries were contracted with a KCl-enriched (50mM) solution. The endothelial-dependent relaxation was evaluated after addition of increasing doses of acetylcholine.


The analysis of morphological parameters showed that mesenteric micro-arteries isolated from n-3 PUFA depleted-KO mice supplemented with PRE (KO-DEF-PRE) present an significant increasing by 20% in mean diameter and develop also an significant increasing by 35% in the basal tone compared to vessels from other groups (KO-DEF or WT-DEF). Similarly, KO-DEF-PRE micro-arteries contracted significantly more to KCl-enriched solution than vessels isolated from other groups. Finally, we measured the relaxation evoked by acetylcholine: KO-DEF-PRE micro-arteries relaxed significantly more compared to KO-DEF mice isolated micro-arteries (61.27±0.343 %KCl max vs 80.513±2.542 %KCl max, p<0.01). This effect was blunted in the presence of COX inhibitor, indomethacin.


Our results suggest that fifteen days of prebiotic supplementation is sufficient to alter morphological and contractile parameters in the mesenteric bed. Importantly, prebiotic supplementation is also able to prevent the endothelial dysfunction observed in KO-DEF mice, independently of the contractile modifications. Results obtained in the presence of indomethacin appoint prostanoids as possible molecular targets, in addition to the NO/NOS pathway. Further analyses are now performed to relate changes in gut functions to cardiovascular alterations.



This work was supported by the FRS-FNRS (Fonds de la Recherche Scientifique) (Convention1.5121.12)

Authors’ Affiliations

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium
Pole of Pharmacology and Therapeutics, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium


  1. Pachikian BD, Neyrinck AM, Cani PD, Portois L, Deldicque L, De Backer FC, Bindels LB, Sohet FM, Malaisse WJ, Francaux M, et al: Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition. BMCPhysiol. 2008, 8: 21-Google Scholar
  2. Pachikian BD, Essaghir A, Demoulin JB, Catry E, Neyrinck AM, Dewulf EM, Sohet FM, Portois L, Clerbaux LA, Carpentier YA, et al: Prebiotic approach alleviates hepatic steatosis: implication of fatty acid oxidative and cholesterol synthesis pathways. Molecular nutrition & food research. 2013, 57 (2): 347-359. 10.1002/mnfr.201200364.View ArticleGoogle Scholar


© Catry et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


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