Deciphering the Role of Dietary Fatty Acids on Extracellular Vesicles-mediated Intercellular Communication

NCT ID: NCT06051461

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2027-09-01

Brief Summary

Dietary interventions have been consistently proposed as a part of a comprehensive strategy to lower the incidence and severity of atherosclerosis and coronary vascular disease. Excessive comsumption of fats enriched in saturated fatty acids (SFAs) is associated with an increased risk of atherosclerosis and other cardiovascular diseases (CVD). In contrasts, replacement of SFAs with monounsaturated fatty acids (MUFAs) and omega-3 long chain polyunsaturated fatty acids (ω3-LCPUFAs) has been reported to be inversely associated with risk of atherosclerosis. This is partly due to the ability of MUFAs (and ω3-LCPUFAs) to modulate lipoprotein composition, oxidation state, and consequently their functionality, among others. While most of the nutritional studies have focused on elucidating the mechanisms by which dietary fats affect lipoprotein particles, little or nothing is known about the regulatory effect of dietary fatty acids on extracellular vesicles (EVs). EVs are small phospholipid particles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role in health and disease. For the first time, the purpose of this project is to establish whether the type of major fatty acids present on a diet (SFAs, MUFAs, or ω3-LCPUFAs) may alter the structure, cargo, and functionality of postprandial- and long-term-EVs. In the precision nutrition era, the investigators expect to offer a new insight on EVs and their relationship with dietary fatty acids through the following objectives: 1) To map changes in the lipidome, proteome, microtranscriptome, and functional properties of circulating EVs in healthy subjects and patients with metabolic syndrome (MetS) both at fasting and at postprandial state upon a challenge of a meal rich in SFAs, MUFAs, and ω3-LCPUFAs; 2) To analyse the contribution of postprandial triacylglyceride-rich lipoproteins (TRL) on EVs-mediated intercellular communication in a fatty acid-dependent manner; and 3) To determine the influence of diets rich in SFAs, MUFAs, and ω3-LCPUFAs on EVs in an animal model of atherosclerosis in the setting of MetS. Collectively, this project will provide fundamental insight into EV biology, and remarks the clinical and functional relevance and divergent consequences of dietary fatty acids in health and disease.

Conditions

Obesity; Metabolic Syndrome; Metabolic Disorder; Inflammation; Immune System and Related Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Metabolic Syndrome patients

Group Type: ACTIVE_COMPARATOR

Oral lipid emulsions

Intervention Type: DIETARY_SUPPLEMENT

The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFAs) or refined olive oil (MUFAs) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA (ω3-LCPUFAs).

Healthy patients

Group Type: EXPERIMENTAL

Oral lipid emulsions

Intervention Type: DIETARY_SUPPLEMENT

The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFAs) or refined olive oil (MUFAs) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA (ω3-LCPUFAs).

Interventions

Oral lipid emulsions

The oral lipid emulsions will contain water, sucrose, emulsifier, flavouring, and the corresponding fat (50 g/m2 of body surface area): milk cream (SFAs) or refined olive oil (MUFAs) with or without a dose of omega-3 PUFA, which will consist of 920 mg of EPA and 760 mg of DHA (ω3-LCPUFAs).

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of metabolic syndrome

Exclusion Criteria

• Allergy to dairy products
• Allergy to fish oil
• Vegetarian
• Tobacco smoker
• Current or recent (<4 wk) use of fish oil supplements or more than four times fish/week
• Received innoculations within 2 mo of starting the study or planned to during the study
• Donated or intended to donate blood from 2 mo before the study till 2 mo after the study
• Unstable body weight (no weight gain/loss >3 kg)

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Spanish National Research Council

OTHER_GOV

Sponsor Role: collaborator

University of Seville

OTHER

Sponsor Role: lead

Responsible Party

Sergio Montserrat de la Paz

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Seville

Seville, Seville, Spain

Countries

Spain

Other Identifiers

US

Identifier Type: -

Identifier Source: org_study_id