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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Metabolic Syndrome X

Intervention / Treatment
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* Other: Medium-chain triglycerides
* Other: Corn oil


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medium-chain triglycerides<br>During 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. | Other: Medium-chain triglycerides<br>* During 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.<br>|
| Active Comparator: Corn oil<br>During 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. | Other: Corn oil<br>* During 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in duodenal expression of genes that regulate intestinal lipid absorption. | 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). | At week 4 and week 10 (at the end of the two 4-weeks supplementation). | 
| Changes in duodenal expression of genes that regulate intestinal lipid synthesis. | 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). | At week 4 and week 10 (at the end of the two 4-weeks supplementation). | 
| 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). |