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Effects of Medium-Chain Triglycerides on Chylomicron Secretion and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With the Metabolic Syndrome

Not Applicable
Completed
Conditions
Metabolic Syndrome X
Interventions
Other: Medium-chain triglycerides
Other: Corn oil
Registration Number
NCT01806142
Lead Sponsor
Laval University
Brief Summary

Several lines of evidence indicate that a significant proportion of cardiovascular disease (CVD) events are attributable to the presence of a cluster of metabolic abnormalities and perturbations, defined as the metabolic syndrome. It has been estimated that approximately 25% of the North American adult population is living with the metabolic syndrome. Recent studies from the investigators group show that overaccumulation of atherogenic triglyceride-rich lipoproteins (TRL) seen in insulin-resistant patients is partly due to increased production rate of intestinally derived apolipoprotein (apo) B-48-containing lipoproteins. This is of interest because substantial evidence exists indicating that elevated levels of intestinal lipoproteins are associated with increased CVD risk. In this regard, there is some evidence that medium-chain triglycerides (MCTs) may beneficially modify lipoprotein metabolism in hypertriglyceridemic patients. However, as emphasized in the body of this grant proposal, the specific impact of MCTs on the intestinal lipoprotein secretion and on expression of genes that regulate intestinal lipid absorption and chylomicron synthesis has not yet been investigated in humans.

The general objective of the proposed research is to investigate the mechanisms by which MCTs beneficially modify intestinal lipoprotein metabolism in patients with the metabolic syndrome. The primary hypothesis is that MCT supplementation will decrease plasma levels of intestinal lipoproteins by reducing secretion of these particles.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
28
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Medium-chain triglyceridesMedium-chain triglyceridesDuring Medium-Chain Triglycerides (MCT period), participant will asked to consume two pastries per day that will provide a total of 20 g of MCT/day for 4 weeks.
Corn oilCorn oilDuring Corn oil period (Control period), participant will asked to consume two pastries per day that will provide a total of 20 g of corn oil/day for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Change in TRL apolipoprotein B48 (apoB-48) production rate.At week 4 and week 10 (at the end of the two 4-weeks supplementation).
Secondary Outcome Measures
NameTimeMethod
Changes in duodenal expression of genes that regulate intestinal lipid absorption.At week 4 and week 10 (at the end of the two 4-weeks supplementation).

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).

Changes in duodenal expression of genes that regulate intestinal lipid synthesis.At week 4 and week 10 (at the end of the two 4-weeks supplementation).

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).

Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48).At week 4 and week 10 (at the end of the two 4-weeks supplementation).

Trial Locations

Locations (1)

Institute of Nutrition and Functional Foods (INAF)

🇨🇦

Quebec, Canada

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