Sympathetic Activation in Obesity
Condition: Obesity; Healthy
MeSH terms: Obesity
Study type: Interventional

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.
    


Intervention name(s): PET Scan; Mixed Meal Test; Muscle sympathetic nerve activity (MSNA); Oral Glucose Tolerance Test; Body Composition, Percent Body Fat & Percent Body Water (Tanita scale); CT Scan; Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)
Intervention type(s): Diagnostic Test; Dietary Supplement; Diagnostic Test; Diagnostic Test; Other; Diagnostic Test; Other
Intervention description(s): Participants will come to the PET Center to undergo the whole body [11C]MRB PET scan. An intravenous bolus dose of MRB (~20mCi) will be injected by an infusion pump. PET data will be acquired dynamically for 120 min using the Siemens mCT-X whole-body PET/CT scanner using continuous bed motion to image multiple PET bed acquisitions from the top of the head to the lower abdominal region.; High Carbohydrate Mixed Meal Test (MMT): participants will be studied after a 10-hour overnight fast. A nurse will insert an intravenous (IV) catheter and subjects will ingest a liquid meal (65% carbohydrate, 20% fat, and 15% protein, corresponding to 40% of daily energy expenditure, in ~16 ounces) to be prepared by the Hospital Research Unit Metabolic Kitchen. Blood samples will be collected at -10, 0, 15, 30, 60, 90, and 120 min) for measurement of glucose, insulin and C-peptide concentrations. Plasma samples will be drawn at baseline and throughout the MMT for measurement of additional hormones (such as thyroid hormones, and catecholamines) and free fatty acids (FFA) levels.; Recording of multiunit postganglionic muscle sympathetic nerve activity (MSNA) will be made from the common peroneal nerve as it winds around the fibular head with the subject in the supine position with the subject's thigh comfortably supported. This procedure requires to first trace the course of the nerve using small electrical stimuli applied to the surface of the skin over the nerve or use of ultrasound to visually assist.; Following a 10-hour overnight fast, a nurse will insert an intravenous (IV) catheter. Subsequently, subjects will ingest 7.5 oz of Glucola, which contains 75 g of dextrose in orange flavored water. Blood samples will be taken at -15, 0, 10, 20, 30, 60, 90 and 120 minutes (after glucola ingestion) for the measurement of plasma glucose, insulin, and C-peptide concentrations, and calculation of measurements of insulin sensitivity index (Matsuda Index). Approximately 40 mL of blood will be drawn at this visit.; will be assessed using bioelectrical impedance analysis Tanita® scale; which is a special multi frequency segmental body composition analyzer that delivers a very mild electrical current that allows measurement of fat mass, percent body fat, fat free mass, total body water, and percent body water. This test will be performed at screening visit.; A CT scan will be performed for attenuation correction and to help delineate the BAT and other regions of interest (ROIs). Images will be reconstructed with an ordered subset expectation maximization algorithm using point spread function correction and time-of-flight information. To delineate fat (WAT, BAT) and skeletal muscle regions of interests (ROIs), CT images are first resliced to match the resolution and location of PET images. As performed in previous studies 2, a supraclavicular ROI is first manually drawn on the CT images. Within that area, the fat ROI is segmented using the CT images and an intensity window from -200 to -50 HU. Subsequently the fat ROI is segmented into WAT and BAT ROIs by using the 11C-MRB PET images: Standardized Uptake Value (SUV) ≥ 1.25 for BAT, SUV < 1.25 for WAT.; For better accuracy, measurement of percent fat and percent body water will be obtained with whole body Dual X-Ray Absorptiometry (DXA) scan (Hologic®) on screening-OGTT visit. The scanner arm will move over the participant's body from feet to head. The machine uses a small amount of radiation (one tenth of the amount of radiation from a chest x-ray) to measure body fat, muscle and bone density.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science