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

Not Applicable

Not yet recruiting

• Conditions: Metabolic Disorder; Inflammation; Obesity; Metabolic Syndrome; Immune System and Related Disorders
• Interventions: Dietary Supplement: Oral lipid emulsions

• Registration Number: NCT06051461
• Lead Sponsor: University of Seville

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-09
• Study First Submitted: 2023-09-05
• Study First Submitted QC: 2023-09-19
• Last Update Submitted: 2023-09-19
• Study First Posted: 2023-09-25
• Last Update Posted: 2023-09-25
• Study Start: 2023-11-01
• Primary Completion: 2024-09-01
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Metabolic Syndrome patients	Oral lipid emulsions	-
Healthy patients	Oral lipid emulsions	-

Primary Outcome Measures

Name	Time	Method
Evolution of cytokines in postprandial state	Up to 6 hours	Pro-inflammatory and anti-inflammatory cytokines, including NFα, IL-1β, IL-6, IL-8, IL-10, ICAM-1, MCP-1, leptin, and adiponectin, in plasma will be measured using appropriate methods (EIA, ELISA, and/or Bioplex multiplex system) (mg/dl).
Evolution of inflammatory markers in postprandial state. [Time Frame: Up to 6 hours]	Up to 6 hours	The acute phase protein (hsCRP), PAI-1, fibrinogen, transferrin, albumin, and myeloperoxidase (MPO) will be measured using appropriate methods (EIA, ELISA, and/or Bioplex multiplex system) (mg/dl).
EV proteome	Up to 6 hours	The quantification of exosome-derived proteins will be performed by nLC-MS/MS
Ev microtranscriptome	Up to 6 hours	Enriched RNA and miRNA derived from exosomes will be determined by Next Generation Sequencing (NGS)
Effect of EVs on gene expression in PBMCs	Up to 6 hours	PBMCs will be isolated from the subjects' peripheral blood and treated with autologous circulating EVs for different times.
EV lipidome	Up to 6 hours	The analysis of intact lipids derived from exosomes will be performed by LC-MS

Trial Locations

Locations (1)

University of Seville; 🇪🇸 Seville, Spain