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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
28
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.
Institute of Nutrition and Functional Foods (INAF)
Québec, Quebec, Canada
Change in TRL apolipoprotein B48 (apoB-48) production rate.
Time frame: 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 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).
Time frame: 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).
Time frame: 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).
Time frame: At week 4 and week 10 (at the end of the two 4-weeks supplementation).
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