Body Weight, Sleep, and Heart Health

A multidisciplinary investigation examining the circadian mechanisms regulating cardiovascular (CV) risk in obesity. Specifically, in a valid circadian protocol, the investigators aim to study resting cardiovascular risk markers and the reactivity of circadian rhythms in these risk markers to standardized stressors in obesity. Furthermore, using an ingenious approach, the investigators propose to explore impairment in pre/post synaptic function in the cardiac left ventricle.

Overall, these studies will help us answer whether CV rhythms predispose obese individuals to increased CV disease risk - particularly around the vulnerable morning period. The results will serve as a foundation for clinical trials of appropriately timed dosing of medications targeting aspects of the CV system in obesity that increase effectiveness while decreasing side-effects.

Healthy lean controls [18.5<BMI<25 kg/m2 and WC <94/80 (men and women respectively)] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water).

Healthy obese [30≤BMI<40 and waist circumference (WC) ≥94/80 (men and women respectively)] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water).

11C-meta-hydroxyephedrine will be used during PET imaging to measure cardiac presynaptic norepinephrine transporter function.

Cardiac beta adrenergic receptor density will be measured via PET imaging with infusion of 11C-CGP12177.

1. Determine in lean healthy humans if coronary microvascular function, measured as coronary microvascular blood flux, has an endogenous circadian rhythm with lowest function in the morning. 2. Test the hypothesis that people with obesity have impaired coronary microvascular blood flux compared to lean individuals, with the exaggerated impairment during the morning. Measured using myocardial contrast echocardiography.

Inclusion Criteria: Ages 25-65 Lean and overweight (BMI 18.5-40kg/m2) Habitually sedentary Exclusion Criteria: History of smoking/tobacco use Insomnia Moderate to severe obstructive sleep apnea. Prior shift work within 6 months prior to the study. Prescription medications Drugs of abuse Acute, chronic, or debilitating medical condition (including diabetes, hypertension, and metabolic syndrome)