Clinical trial NCT01934543: Effects of Polyunsaturated Fatty Acids on Intestinal Lipid Metabolism in Insulin-resistant Men
Official title: Differential Effects of Saturated and Polyunsaturated Fatty Acids on Chylomicron Secretion and Expression of Key Genes and Proteins That Regulate Intestinal Lipid Metabolism in Men With Dyslipidemia Associated With Insulin-resistance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Lead sponsor: Laval University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2013-09-04
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The overaccumulation of apolipoprotein (apo)B-48-containing lipoproteins of intestinal origin observed in patients with insulin-resistance is now thought to be attributable to both elevated intestinal production and reduced clearance of these lipoproteins. Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease (CVD) risk. Therefore, reduction of atherogenic plasma TRL levels of intestinal origin appears to be crucial to improve CVD risk associated with insulin-resistance. In this regard, there is some evidence that the clinical recommendation to replace dietary saturated fatty acids (SFAs) by n-6 polyunsaturated fatty acids (PUFAs) reduces CVD risk in the general population. Although the beneficial impact of n-6 PUFAs on CVD risk has been related primarily to favorable changes in plasma LDL-cholesterol levels, recent data suggest that chronic n-6 PUFA consumption may also exert beneficial effects on CVD risk by reducing postprandial lipemia. The impact of substituting SFAs by n-6 PUFAs on postprandial lipid response may be of even greater significance in dyslipidemic patients with insulin-resistance among whom intestinal triglyceride-rich lipoproteins (TRLs) represent a large proportion of the atherogenic lipoproteins. The general objective of the proposed research is to investigate how dietary n-6 PUFAs in place of SFAs modify intestinal lipoprotein metabolism in men with dyslipidemia associated with insulin-resistance. The investigators hypothesize that the intestinal secretion of apoB-48-containing lipoproteins will be lower following a diet rich in n-6 PUFAs than after consuming a diet rich in SFAs. The investigators also hypothesize that substitution of SFAs by n-6 PUFAs will be associated with significant alterations in expression of key genes and proteins involved in intestinal lipoprotein metabolism.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in TRL apolipoprotein B48 (apoB-48) production rate.
timeFrame: At week 4 and week 12 (at the end of the two 4-weeks diets).
Secondary outcomes:
measure: Changes in duodenal expression of genes that regulate intestinal lipid absorption.
timeFrame: At week 4 and week 12 (at the end of the two 4-weeks diets).
measure: Changes in duodenal expression of genes that regulate intestinal lipid synthesis.
timeFrame: At week 4 and week 12 (at the end of the two 4-weeks diets).
measure: Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48).
timeFrame: At week 4 and week 12 (at the end of the two 4-weeks diets).
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: Institute of Nutrition and Functional Foods (INAF)
Study officials:
affiliation: Laval University
name: Patrick Couture, MD,FRCP,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drouin-Chartier JP, Tremblay AJ, Lepine MC, Lemelin V, Lamarche B, Couture P. Substitution of dietary omega-6 polyunsaturated fatty acids for saturated fatty acids decreases LDL apolipoprotein B-100 production rate in men with dyslipidemia associated with insulin resistance: a randomized controlled trial. Am J Clin Nutr. 2018 Jan 1;107(1):26-34. doi: 10.1093/ajcn/nqx013.