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 (MCT)

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

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

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.

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.

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.

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.

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.

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).

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).

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.

Tremblay AJ, Lamarche B, Labonte ME, Lepine MC, Lemelin V, Couture P. Dietary medium-chain triglyceride supplementation has no effect on apolipoprotein B-48 and apolipoprotein B-100 kinetics in insulin-resistant men. Am J Clin Nutr. 2014 Jan;99(1):54-61. doi: 10.3945/ajcn.113.068767. Epub 2013 Oct 30.