Effects of Monounsaturated Fatty Acids on Intestinal Lipid Metabolism in Insulin Resistant Subjects (MUFA )

• ClinicalTrials.gov Identifier: NCT03872349
• Recruitment Status: Recruiting
• First Posted: March 13, 2019
• Last Update Posted: September 1, 2021
• Sponsor: Laval University
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Patrick Couture, Laval University

Study Description

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 triglyceride-rich lipoproteins à (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 monounsaturated fatty acids (MUFAs) reduces CVD risk in the general population. Although the beneficial impact of PUFAs on CVD risk has been related primarily to favorable changes in plasma LDL-cholesterol levels, recent data suggest that chronic MUFA consumption may also exert beneficial effects on CVD risk by reducing postprandial lipemia. The impact of substituting SFAs by MUFAs on postprandial lipid response may be of even greater significance in dyslipidemic patients with insulin-resistance among whom intestinal TRLs represent a large proportion of the atherogenic lipoproteins. The general objective of the proposed research is to investigate how dietary MUFAs in place of SFAs modify intestinal lipoprotein metabolism in men and women 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 MUFAs than after consuming a diet rich in SFAs. The investigators also hypothesize that substitution of SFAs by MUFAs will be associated with significant alterations in expression of key genes and proteins involved in intestinal lipoprotein metabolism.

Condition or disease	Intervention/treatment	Phase
Metabolic Syndrome	Other: Monounsaturated fatty acids diet; Other: Saturated fatty acids diet	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Differential Effects of Saturated and Monounsaturated Fatty Acids on Chylomicron Secretion and Expression of Key Genes That Regulate Intestinal Lipid Metabolism in Insulin Resistant Subjects
• Actual Study Start Date: January 9, 2020
• Actual Primary Completion Date: August 19, 2021
• Estimated Study Completion Date: August 19, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Monounsaturated fatty acids diet; During 4 weeks, subjects eat a diet high in monounsaturated fatty acids (percent of total caloric intake: 15.0% from proteins; 50.0% from carbohydrates; 35.0% from fat: 7.1% from saturated fat; 20.7% from monounsaturated fat; 7.2% from n-6 polyunsaturated fat).	Other: Monounsaturated fatty acids diet; During 4 weeks, subjects eat a diet high in monounsaturated fatty acids and will have a duodenal gastroscopy and a kinetic study at the end of the 4-week period.; Other: Saturated fatty acids diet; During 4 weeks, subjects eat a diet high in saturated fatty acids and will have a duodenal gastroscopy and a kinetic study at the end of the 4-week period.
Experimental: 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; 14.4% from monounsaturated fat; 7.2% from n-6 polyunsaturated fat).	Other: Monounsaturated fatty acids diet; During 4 weeks, subjects eat a diet high in monounsaturated fatty acids and will have a duodenal gastroscopy and a kinetic study at the end of the 4-week period.; Other: Saturated fatty acids diet; During 4 weeks, subjects eat a diet high in saturated fatty acids and will have a duodenal gastroscopy and a kinetic study at the end of the 4-week period.

Outcome Measures

Primary Outcome Measures :

1. Change in TRL apolipoprotein B48 (apoB-48) production rate. [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets) ]

Secondary Outcome Measures :

1. Changes in duodenal expression of Niemann-Pick C1-like 1, Adenosine triphosphate-binding cassette transporters, Fatty Acid Binding Protein, Sterol Regulatory Element Binding Protein. [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets) ]
2. Changes in duodenal expression of diacylglycerol acyltransferase, Acyl-CoA:cholesterol O-acyltransferase 2 and 3-hydroxy-methylglutaryl-CoA reductase. [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets) ]
3. Change in synthesis of apoB-48 containing lipoproteins (Microsomal triglyceride transfer protein (MTP), apoB-48). [ Time Frame: At week 4 and week 12 (at the end of the two 4-weeks diets) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men and women aged between 18-60 years
• Waist circumference > 102 cm (men) and > 88 cm (women)
• HDL-cholesterol < 1.1 mmol/L (men) and < 1.3 mmol/L (women)
• Triglycerides > 1.7 mmol/L
• Fasting blood glucose > 6.1 mmol/L
• Normal blood pressure (<130/85)

Exclusion Criteria:

• Men and women < 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.

Contacts and Locations

Contacts

Contact: Patrick Couture, MD, FRCP, PhD; 418-654-2106; patrick.couture@crchul.ulaval.ca

Contact: André Tremblay, PhD; 418-656-2131 ext 411417; andre.tremblay@fsaa.ulaval.ca

Locations

Canada

Institute of Nutrition and Functional Foods (INAF); Recruiting

Quebec, Canada, G1V 0A6

Contact: Patrick Couture, MD, FRCP,PhD 418-654-2106 patrick.couture@crchul.ulaval.ca

Contact: André Tremblay, PhD 418-656-2131 ext 411417 andre.tremblay@fsaa.ulaval.ca

Principal Investigator: Patrick Couture, MD,FRCP,PhD

Sub-Investigator: André Tremblay, PhD

Sponsors and Collaborators

Laval University

Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Patrick Couture, MD, FRCP, PhD; Laval University

More Information

• Responsible Party: Patrick Couture, Principal Investigator, Laval University
• ClinicalTrials.gov Identifier: NCT03872349
• Other Study ID Numbers: INAF-MUFA
• First Posted: March 13, 2019
• Last Update Posted: September 1, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Metabolic Syndrome; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases