Sympathetic Activation in Obesity

Not Applicable

Completed

Conditions: Obesity
Healthy

Interventions: Diagnostic Test: PET Scan
Dietary Supplement: Mixed Meal Test
Diagnostic Test: Muscle sympathetic nerve activity (MSNA)
Diagnostic Test: Oral Glucose Tolerance Test
Other: Body Composition, Percent Body Fat & Percent Body Water (Tanita scale)
Diagnostic Test: CT Scan
Other: Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)

Registration Number: NCT04946552

Lead Sponsor: Yale University

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

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
Radiation works or participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits.
Subjects with history of IV drug use which would prevent venous access for PET tracer injection
Severe motor problems that prevent the subject from lying still for PET and MR imaging
Subjects who complain of chronic pain
Blood donation within 8 weeks of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Individuals with normal BMI	Oral Glucose Tolerance Test	(BMI 18-25 kg/m2)
Individuals with normal BMI	Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)	(BMI 18-25 kg/m2)
Individuals with obesity	Oral Glucose Tolerance Test	(BMI 30-40 kg/m2)
Individuals with normal BMI	PET Scan	(BMI 18-25 kg/m2)
Individuals with normal BMI	Mixed Meal Test	(BMI 18-25 kg/m2)
Individuals with normal BMI	Muscle sympathetic nerve activity (MSNA)	(BMI 18-25 kg/m2)
Individuals with obesity	Muscle sympathetic nerve activity (MSNA)	(BMI 30-40 kg/m2)
Individuals with obesity	Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)	(BMI 30-40 kg/m2)
Individuals with normal BMI	Body Composition, Percent Body Fat & Percent Body Water (Tanita scale)	(BMI 18-25 kg/m2)
Individuals with obesity	PET Scan	(BMI 30-40 kg/m2)
Individuals with normal BMI	CT Scan	(BMI 18-25 kg/m2)
Individuals with obesity	Mixed Meal Test	(BMI 30-40 kg/m2)
Individuals with obesity	Body Composition, Percent Body Fat & Percent Body Water (Tanita scale)	(BMI 30-40 kg/m2)
Individuals with obesity	CT Scan	(BMI 30-40 kg/m2)

Primary Outcome Measures

Name	Time	Method
Microneurography (Muscle Sympathetic Nerve Activity (MSNA)) Measured by Burst Frequency	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.
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System	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.

Secondary Outcome Measures

Name	Time	Method
C-Peptide	2 hours	Plasma samples will be drawn at baseline and throughout the MMT for measurement of C-Peptide. The normal range for C-Peptide is 0.80 - 3.85 ng/mL
Thyroid Function Tests	2 hours	Plasma samples will be drawn at baseline and throughout the mixed meal test (MMT) for measurement of Thyroid Stimulating Hormone (TSH), free T4 (FT4) and total T3 (TT3). The normal range for TSH is : 0.4-4.5 mlU/L, FT4: 0.8-1.8 ng/dL, TT3: 76 - 181 ng/dL.
Electrocardiogram (EKG) - RR Interval	30-60 minutes	EKG surface electrodes will be applied to the chest for measurement of RR interval.
DVR of Norepinephrine Transporter (NET) in the Central Nervous System (CNS)	120 minutes	Regional quantification of \[11C\]MRB uptake as distribution volume ratio (DVR ) will be used to measure NET in the CNS.
Insulin Levels	2 hours	Measurement of plasma insulin levels will be obtained at fasting and during the MMT. Insulin levels in the plasma are higher in individuals with obesity. The normal range for insulin is: \< or = 19.6 mcg/dL
Plasma Free Fatty Acids (FFA)	2 hours	Percent of plasma free fatty acids levels will be obtained at fasting and during the Mixed Meal Test (MMT). FFA levels in the plasma are higher in individuals with obesity than individuals with normal weight.
Plasma Glucose	2 hours	Measurement of plasma glucose levels will be obtained at fasting and during the Mixed Meal Test (MMT). The normal range for glucose levels is 70-100 mg/dL.
Plasma Catecholamines (Epinephrine and Norepinephrine)	2 hours	Measurement of epinephrine and norepinephrine levels in the plasma at fasting and during the MMT. The normal range for epinephrine is 0 to 140 pg/mL (764.3 pmol/L). The normal range for norepinephrine is 70 to 1700 pg/mL (413.8 to 10048.7 pmol/L).
DVR of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System After Mixed Meal Test	120 minutes	Measurement of peripheral SNS Activity with \[11C\]MRC for PET/CT before (fasting) and after a high carbohydrate mixed meal in individuals with normal weight and obesity.
Electrocardiogram (EKG)- Heart Rate	30-60 minutes	EKG surface electrodes will be applied to the chest for measurement of heart rate and heart rate variability (QT Interval).