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 show that overaccumulation of atherogenic triglyceride-rich lipoproteins (TRL) seen in insulin-resistant patients is partly due to increased production rate of intestinally derived apolipoproteinB-48-containing lipoproteins. This is of interest because substantial evidence exists indicating that elevated levels of intestinal lipoproteins are associated with increased CVD risk. However, as indicated in the body of this grant proposal, the underlying mechanisms that lead to intestinal overproduction of lipoproteins in insulin-resistant states are poorly understood. The general objective of the proposed research is to investigate the mechanisms by which the metabolic syndrome affects apolipoproteinB-48 secretion in human. The primary hypothesis is that insulin resistance will be associated with higher levels of intestinal lipoproteins because of an increased secretion of these particles.
Study Type
OBSERVATIONAL
Enrollment
30
Institute of Nutrition and Functional Foods (INAF)
Québec, Quebec, Canada
Change in TRL apolipoproteinB-48 production rate.
Time frame: Week 1
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)
Time frame: Week 1
Change 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-transferase 2 (ACAT2) and 3-hydroxy-methylglutaryl-CoA reductase (HMG CoA reductase).
Time frame: Week 1
Change in synthesis of apolipoproteinB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apolipoproteinB-48).
Time frame: Week 1
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