Adipocyte-Derived Extracellular Vesicles, Weight Loss, and Endothelial Function

Adipocyte-Derived Extracellular Vesicles; Novel Biomarker and Mediator of Obesity-Related Endothelial Dysfunction

Changes in adipose tissue biology are now recognized as a key factor underlying the increased risk of metabolic and cardiovascular disease with obesity. Clinical interest in adipocyte-derived extracellular vesicles (Ad-EVs) has intensified due to their potential as circulating biomarkers of adipose tissue health and systemic messengers, regulators and mediators of cardiometabolic health and disease with obesity.

The investigators hypothesize that elevated Ad-EVs in adults with obesity will be negatively associated with endothelium-dependent vasodilation. Furthermore, the investigators hypothesize that in adults with obesity, intentional weight loss-induced reduction in circulating Ad-EVs is associated with greater endothelium-dependent vasodilation.

Inclusion criteria:

• Age ≥40 years
• BMI <25 kg/m2 and BMI >25 kg/m2 for Phase 1 and BMI >25 kg/m2 for Phase 2. Rationale for defining obesity as BMI >25 kg/m2

Exclusion criteria:

• Current smoker
• Chronic overt medical condition (e.g., evidence of coronary artery disease on resting ECG, any history of myocardial infarction or stroke, or cancer, diabetes based on fasting blood glucose concentration)
• Alcohol abuse or dependence defined as more than 14 standard drinks/week and no more than 4 standard drinks/day for men and 7 standard drinks/week and 3 standard drinks/day for women (a standard drink is defined as 12 ounces of beer, 5 ounces of wines, 1 ½ ounces of 80-proof distilled spirits) reported during the medical history/physical exam
• Stage III hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg)
• Regular vigorous aerobic/endurance exercise (>3 bouts/week, >30 minutes/bout at a workload >6 METS)
• Women who are pregnant or breastfeeding
• History of anaphylaxis to betadine, lidocaine, iodine
• Raynaud's disease
• History of clotting disorders
• Anyone taking blood thinners and clotting medications
• Anyone taking statin medication
• Planned pregnancy in coming 4-6 months