Study of the Relationships Between Apolipoprotein B-48 Kinetics and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With the Metabolic Syndrome (SMB48)

Study Overview
=================
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 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.

Official Title
-----------------
Study of the Relationships Between Apolipoprotein B-48 Kinetics and Expression of Genes That Regulate Intestinal Lipid Metabolism in Men With the Metabolic Syndrome.

Conditions
-----------------
Metabolic Syndrome X

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with metabolic syndrome: Men aged between 18-60 years Waist circumference >102 HDL-cholesterol < 1.1 mmol/L Triglycerides > 1.7 mmol/L Fasting blood glucose >6.1 mmol/L Normal blood pressure (<130/85) Controls: Men aged between 18-60 years Waist circumference >102 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
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TRL apolipoproteinB-48 production rate. |  | Week 1 | 

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) | 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). | Week 1 | 
| Change in synthesis of apolipoproteinB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apolipoproteinB-48). |  | Week 1 |