Role of Adiposomes in Endothelial Dysfunction

Part of paid clinical trials in Chicago, Illinois.

Sponsor
University of Illinois at Chicago
Study ID
NCT05199454
Status
Recruiting
Apply to this trial

Conditions

  • Cardiovascular Diseases
  • Diabetes
  • Obesity

Eligibility Criteria

Sex
ALL
Age
18 Years - 50 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
May 16, 2022
Status verified
Jan 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
60 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Experimental: Exercise training
    Aerobic exercise training for 12 weeks, 3 times per week, 60 minutes per session.
  • No Intervention: Control (standards of care)
    This arm will receive brochures for healthy lifestyle recommendations. No intervention will be conducted.

Primary Outcome Measure

Brachial artery flow-mediated dilation (percent vasodilation) in 60 obese diabetic subjects [ Time Frame: 4 years ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of Illinois at ChicagoChicagoIllinois60612
Abeer M Mohamed, MD, PhD
[email protected]
312-355-8099

Find similar trials in Chicago, IL

By condition
Obesity / overweight
By specialty
EndocrinologyMetabolic healthWeight loss
By research site
University of Illinois at Chicago· Chicago, IL

Related Studies