Role of Adiposomes in Endothelial Dysfunction

University of Illinois

Status: Enrolling

Conditions: Diabetes; Obesity; Cardiovascular Diseases

Treatments: Other: Exercise training

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05199454

1R01HL161386-01 (U.S. NIH Grant/Contract)

2021-1113

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Exercise training

Experimental group

Description:

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

Treatment:

Other: Exercise training

Control (standards of care)

No Intervention group

Description:

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