Effects of Polyunsaturated Fatty Acids on Intestinal Lipid Metabolism in Insulin-resistant Men

Metabolic Syndrome Clinical Trial

— PUFA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01934543
• Other study ID #: INAF-PUFA
• Status: Completed
• Phase: N/A
• First received: August 30, 2013
• Last updated: September 7, 2016
• Start date: January 2014
• Est. completion date: May 2016

Study information

• Verified date: September 2016
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: May 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X

Intervention

Other:
• Polyunsaturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 6.0% from saturated fat; 14.4% from monounsaturated fat; 12.6% from n-6 polyunsaturated fat).
• Saturated fatty acids diet
During 4 weeks, subjects eat a diet high in polyunsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 13.4% from saturated fat; 15.3% from monounsaturated fat; 4.0% from n-6 polyunsaturated fat).

Locations

Country	Name	City	State
Canada	Institute of Nutrition and Functional Foods (INAF)	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Laval University	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in TRL apolipoprotein B48 (apoB-48) production rate.		At week 4 and week 12 (at the end of the two 4-weeks diets).	No
Secondary	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).	At week 4 and week 12 (at the end of the two 4-weeks diets).	No
Secondary	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).	At week 4 and week 12 (at the end of the two 4-weeks diets).	No
Secondary	Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48).		At week 4 and week 12 (at the end of the two 4-weeks diets).	No