Role of Adiposomes in Endothelial Dysfunction

NCT ID: NCT05199454

Last Updated: 2025-01-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-16
• Study Completion Date: 2026-12-31

Brief Summary

The development of type II diabetes (T2D) is strongly associated with obesity and both are well-established risk factors for cardiovascular disease. Knowing that vascular dysfunction is an early event in the development of cardiovascular disease in obese diabetic (OB-T2D) patients, The investigators set their long-term goal to define molecular mechanisms of vascular dysfunction and corrective strategies that target these mechanisms such as physical activity and weight loss. The investigators recently discovered that human adipose tissues release extracellular vesicles (adiposomes) that are efficiently captured by endothelial cells. Adiposomes are known to carry bioactive cargos such as proteins and micro RNAs; however, their lipid content has not been studied nor has their ability to transfer their lipid cargo to endothelial cells. In the current application, the investigators propose to investigate the role of adiposomes in communicating the unhealthy milieu, mainly dysregulated lipids, to endothelial cells in OB-T2D subjects. On top of these lipid species that the investigators propose to be carried by adiposomes are glycosphingolipids (GSLs). These lipids originate from the glycosylation of ceramides, a chemical process that is upregulated in the presence of inflammation and high glucose levels. Preliminary findings showed that in endothelial cells, GSL-rich adiposomes disturb plasma membrane structure and subsequently induce endothelial dysfunction. Moreover, the investigators found that preconditioning endothelial cells with high shear stress (which is an exercise mimetic) protected endothelial cells from the detrimental effects induced by adiposomes. Therefore, the central hypothesis is that adipose tissues in OB-T2D patients release GSL-loaded adiposomes that induce vascular endothelial dysfunction. The researchers propose that exercise and weight loss interventions (bariatric surgery) will restore adipose tissue homeostasis, reduce GSL-loaded adiposomes, and subsequently alleviate vascular risk in OB-T2D patients. The investigators will test the hypotheses by pursuing the following aims: aim 1: Investigate the role of GSL-rich adiposomes in the pathogenesis of endothelial dysfunction in OB-T2D adults; aim 2: Test the effectiveness of exercise training in reducing adiposome-mediated effects on vascular function; and aim 3: Examine changes in adiposome/caveolae axis following metabolic surgery and their association with vascular function.

Conditions

Obesity; Diabetes; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Exercise training

Aerobic exercise training for 12 weeks, 3 times per week, 60 minutes per session.

Group Type: EXPERIMENTAL

Exercise training

Intervention Type: OTHER

Aerobic exercise training using a treadmill or a bike for 12 weeks, 3 times per week, 60 minutes per session.

Control (standards of care)

This arm will receive brochures for healthy lifestyle recommendations. No intervention will be conducted.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Exercise training

Aerobic exercise training using a treadmill or a bike for 12 weeks, 3 times per week, 60 minutes per session.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• BMI ≥ 35 kg/m2
• Between ages 18-50 years
• Not pregnant
• Diabetic (Current use of diabetes medication or fasting glucose ≥126 mg/dL)
• Medical clearance to participate in a moderate-intensity exercise program

Exclusion Criteria

• Pregnant women
• Current smokers
• Currently abusing alcohol or drugs
• Chronic heart, liver, or kidney diseases, autoimmune diseases, or cancer
• Non-English speakers
• History of allergic reactions to lidocaine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Abeer M. Mohamed

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abeer M Mohamed, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Abeer M Mohamed, MD, PhD

Role: CONTACT

amahmo4@uic.edu

312-355-8099

Facility Contacts

Abeer M Mohamed, MD, PhD

Role: primary

amahmo4@uic.edu

312-355-8099

Other Identifiers

1R01HL161386-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2021-1113

Identifier Type: -

Identifier Source: org_study_id