Effects of Polyunsaturated Fatty Acids on Intestinal Lipid Metabolism in Insulin-resistant Men (PUFA)
7 septembre 2016 mis à jour par: Patrick Couture, Laval University
Differential Effects of Saturated and Polyunsaturated Fatty Acids on Chylomicron Secretion and Expression of Key Genes and Proteins That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With Insulin-resistance
The overaccumulation of apolipoprotein (apo)B-48-containing lipoproteins of intestinal origin observed in patients with insulin-resistance is now thought to be attributable to both elevated intestinal production and reduced clearance of these lipoproteins.
Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease (CVD) risk.
Therefore, reduction of atherogenic plasma TRL levels of intestinal origin appears to be crucial to improve CVD risk associated with insulin-resistance.
In this regard, there is some evidence that the clinical recommendation to replace dietary saturated fatty acids (SFAs) by n-6 polyunsaturated fatty acids (PUFAs) reduces CVD risk in the general population.
Although the beneficial impact of n-6 PUFAs on CVD risk has been related primarily to favorable changes in plasma LDL-cholesterol levels, recent data suggest that chronic n-6 PUFA consumption may also exert beneficial effects on CVD risk by reducing postprandial lipemia.
The impact of substituting SFAs by n-6 PUFAs on postprandial lipid response may be of even greater significance in dyslipidemic patients with insulin-resistance among whom intestinal triglyceride-rich lipoproteins (TRLs) represent a large proportion of the atherogenic lipoproteins.
The general objective of the proposed research is to investigate how dietary n-6 PUFAs in place of SFAs modify intestinal lipoprotein metabolism in men with dyslipidemia associated with insulin-resistance.
The investigators hypothesize that the intestinal secretion of apoB-48-containing lipoproteins will be lower following a diet rich in n-6 PUFAs than after consuming a diet rich in SFAs.
The investigators also hypothesize that substitution of SFAs by n-6 PUFAs will be associated with significant alterations in expression of key genes and proteins involved in intestinal lipoprotein metabolism.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
30
Phase
- N'est pas applicable
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Quebec, Canada, G1V 0A6
- Institute of Nutrition and Functional Foods (INAF)
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 60 ans (Adulte)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Homme
La description
Inclusion Criteria:
- Men aged between 18-60 years
- Waist circumference > 102 cm
- HDL-cholesterol < 1.1 mmol/L
- Triglycerides > 1.7 mmol/L
- Fasting blood glucose > 6.1 mmol/L
- Normal blood pressure (<130/85)
Exclusion Criteria:
- Women
- Men < 18 or > 60 years
- Smokers (> 1 cigarette/day)
- Body weight variation > 10% during the last 6 months prior to the study baseline
- Subjects with a previous history of cardiovascular disease
- Subjects with type 2 diabetes
- Subjects with a monogenic dyslipidemia
- Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
- Subjects with endocrine or gastrointestinal disorders
- History of alcohol or drug abuse within the past 2 years
- Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Polyunsaturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0%
from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).
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During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0%
from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).
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Expérimental: Saturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0%
from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).
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During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0%
from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
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Change in TRL apolipoprotein B48 (apoB-48) production rate.
Délai: At week 4 and week 12 (at the end of the two 4-weeks diets).
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At week 4 and week 12 (at the end of the two 4-weeks diets).
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Changes in duodenal expression of genes that regulate intestinal lipid absorption.
Délai: At week 4 and week 12 (at the end of the two 4-weeks diets).
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Genes that regulate intestinal lipid absorption that will be measured are Niemann-Pick C1-like 1 (NPC1L1), Adenosine triphosphate(ATP)-binding cassette transporters (ABCG5/8), Fatty Acid Binding Protein (FABP), Sterol Regulatory Element Binding Protein (SREBP-1c).
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At week 4 and week 12 (at the end of the two 4-weeks diets).
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Changes in duodenal expression of genes that regulate intestinal lipid synthesis.
Délai: At week 4 and week 12 (at the end of the two 4-weeks diets).
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Genes that regulate intestinal lipid synthesis that will be measured are Acyl-Coenzyme A(CoA):diacylglycerol acyltransferase (DGAT), Acyl-CoA:cholesterol O-acyltransferase 2 (ACAT2) and 3-hydroxy-methylglutaryl-CoA reductase (HMG CoA reductase).
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At week 4 and week 12 (at the end of the two 4-weeks diets).
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Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48).
Délai: At week 4 and week 12 (at the end of the two 4-weeks diets).
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At week 4 and week 12 (at the end of the two 4-weeks diets).
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Patrick Couture, MD,FRCP,PhD, Laval University
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 janvier 2014
Achèvement primaire (Réel)
1 septembre 2015
Achèvement de l'étude (Réel)
1 mai 2016
Dates d'inscription aux études
Première soumission
30 août 2013
Première soumission répondant aux critères de contrôle qualité
3 septembre 2013
Première publication (Estimation)
4 septembre 2013
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
8 septembre 2016
Dernière mise à jour soumise répondant aux critères de contrôle qualité
7 septembre 2016
Dernière vérification
1 septembre 2016
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- INAF-PUFA
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