Sympathetic Activation in Obesity
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Obesity
- Sponsor
- Yale University
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The primary objective of this study is to determine whether sympathetic nervous system (SNS) activity in white adipose tissue (WAT) and brown adipose tissue (BAT), skeletal muscle and brain is altered in individuals with obesity in comparison to individuals with normal weight. Simultaneous multi-organ SNS activation will be obtained with a radiotracer for norepinephrine transporter (NET) for whole-body Positron Emission Tomography (PET) imaging and microneurography (peroneal muscle SNS activity).
The secondary objectives of this study are: 1) to evaluate whether gender differences affect peripheral SNS in healthy normal weight and obese men and women in adipose tissue (WAT and BAT) and muscle (resting/fasting); 2) To investigate the relationship between peripheral and central SNS activity in obesity, by correlating SNS activity in peripheral tissues (WAT, BAT, and muscle) and brain; and 3) To investigate NET CNS and peripheral SNS activity before and after a high carbohydrate mixed meal in lean and obese men and women.
Investigators
Eligibility Criteria
Inclusion Criteria
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Age 18-45 years
- •In good general health as evidenced by medical history and lean (BMI 18.5-24.9 kg/m2) or non-diabetic obese (BMI 30-50 kg/m2) with a fasting plasma glucose (FPG) \<100 mg/dL and a hemoglobin A1c \<5.7%.
Exclusion Criteria
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Hypertension
- •Cardiac or pulmonary disease,
- •Known history of Type 1 or Type 2 diabetes
- •Hepatic disease, swallowing and gastrointestinal disorders
- •Current use of anti-obesity medications, supplements and/or anti-hyperglycemic medications
- •Neurological injury or illness, and psychiatric medications
- •Women who are pregnant or lactating
- •Subjects who suffer from claustrophobia
- •Subjects who have received a diagnostic or therapeutic radiopharmaceutical within 7 days prior to participation in this study
Outcomes
Primary Outcomes
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System
Time Frame: 120 minutes
Lean individuals with a BMI of 18-25 and obese individuals with a BMI of 30-40 will undergo a PET/CT scan to determine group differences in sympathetic nervous system (SNS) activity in white adipose tissue (WAT), brown adipose tissue (BAT), and deltoid muscle. SNS activity will be determined by using \[11C\]MRB a radiotracer for PET imaging.
Microneurography (Muscle Sympathetic Nerve Activity (MSNA)) Measured by Burst Frequency
Time Frame: 30-60 minutes
Muscle sympathetic nerve activity will be quantified by identification and measurement of sympathetic bursts in the integrated neurogram and expressed as burst frequency (mean number of bursts per unit time) to determinate group differences in peroneal MSNA at baseline (fasting) and during MMT.
Secondary Outcomes
- DVR of Norepinephrine Transporter (NET) in the Central Nervous System (CNS)(120 minutes)
- Insulin Levels(2 hours)
- Plasma Free Fatty Acids (FFA)(2 hours)
- Plasma Glucose(2 hours)
- C-Peptide(2 hours)
- Thyroid Function Tests(2 hours)
- Electrocardiogram (EKG) - RR Interval(30-60 minutes)
- Plasma Catecholamines (Epinephrine and Norepinephrine)(2 hours)
- DVR of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System After Mixed Meal Test(120 minutes)
- Electrocardiogram (EKG)- Heart Rate(30-60 minutes)