Clinical trial NCT05199454: Role of Adiposomes in Endothelial Dysfunction
Official title: Role of Adiposomes in Diabetes-Associated Endothelial Dysfunction and Restorative Effects of Exercise and Metabolic Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obesity
Diabetes
Cardiovascular Diseases
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-01-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Clinical Trial
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Brachial artery flow-mediated dilation (percent vasodilation) in 60 obese diabetic subjects
timeFrame: 4 years
Secondary outcomes:
measure: Glycosphingolipid content (ng/ml) in adiposomes from 60 obese diabetic subjects
timeFrame: 4 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Abeer M Mohamed, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: