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

NCT01934543 | Completed

• 1 other identifier: INAF-PUFA
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in TRL apolipoprotein B48 (apoB-48) production rate.

  At week 4 and week 12 (at the end of the two 4-weeks diets).

Secondary Outcomes (3)

• Changes in duodenal expression of genes that regulate intestinal lipid absorption.

  At week 4 and week 12 (at the end of the two 4-weeks diets).

• Changes in duodenal expression of genes that regulate intestinal lipid synthesis.

  At week 4 and week 12 (at the end of the two 4-weeks diets).

• 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).

Study Arms (2)

Polyunsaturated fatty acids diet

EXPERIMENTAL

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).

Other: Polyunsaturated fatty acids diet

Saturated fatty acids diet

EXPERIMENTAL

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).

Other: Saturated fatty acids diet

Interventions

Polyunsaturated fatty acids diet OTHER

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).

Polyunsaturated fatty acids diet

Saturated fatty acids diet OTHER

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).

Saturated fatty acids diet

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laval University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Institute of Nutrition and Functional Foods (INAF)

Québec, Quebec, G1V 0A6, Canada

Location

Related Publications (1)

• 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.

  PMID: 29381796 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Patrick Couture, MD,FRCP,PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FRCP, PhD

Study Record Dates

• First Submitted: August 30, 2013
• First Posted: September 4, 2013
• Study Start: January 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: May 1, 2016
• Last Updated: September 8, 2016

Record last verified: 2016-09

Locations

CA (1)