# Sympathetic activation in obesity

> **NIH NIH R56** · YALE UNIVERSITY · 2021 · $251,250

## Abstract

Project Summary
Obesity is associated with an increased risk of diabetes and cardiovascular disease.
Sympathetic nervous system (SNS) dysfunction has been described in individuals with
obesity and may be implicated in the pathogenesis of obesity-related comorbidities. SNS
regulates energy homeostasis by promoting a coordinated multi-organ response.
Regionalized SNS hyperactivation of certain organs (fat, skeletal muscle and kidneys) but
not others (adrenal glands, heart) has been observed in individuals with obesity.
Dysfunctional coordination of SNS activation to target organs may explain the increased
risk of cardiometabolic disorders in obesity.
SNS activates target-organs by releasing norepinephrine (NE) which is then recycled
back by pre-synaptic norepinephrine transporters (NET). Whole-body positron emission
tomography (PET) with the radiotracer for norepinephrine transporters ((S,S)-11C-O-
methylreboxetine ([11C]MRB) has been used to quantify NET availability in vivo in humans
and rodents in: a) peripheral tissues (brown and white adipose tissues and skeletal
muscle); and b) in the central nervous system. Studies using [11C]MRB PET imaging
showed that NET-availability in brown adipose tissue (BAT) was reduced in women with
obesity. In addition, [11C]MRB binding in skeletal muscle (deltoid) inversely correlated with
body mass index (BMI) in healthy women. Therefore, to determine whether regionalized
SNS activation of target organs is altered by obesity, healthy men and women with normal
body mass index (BMI) and with obesity will undergo whole body [11C]MRB PET imaging
and microneurography (gold standard test for assessment of muscle SNS activity). To
further investigate the impact of obesity in coordinating SNS multi-organ activation, SNS
activity will be also measured in response to a food challenge. Parallel animal studies will
be performed to clarify the relationship between peripheral and central NET dynamics
and the time course of which each of these NET sources change as obesity develops.
Whole body [11C]MRB PET imaging allows simultaneous multi-organ measurements and
this project will help further understand the impact of obesity in SNS activity. Dysregulated
coordination of SNS activity may play a role in the pathophysiology of obesity-related
cardiometabolic disorders.

## Key facts

- **NIH application ID:** 10412286
- **Project number:** 1R56DK129344-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Renata Da Silva Belfort De Aguiar
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2021-09-12 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412286

## Citation

> US National Institutes of Health, RePORTER application 10412286, Sympathetic activation in obesity (1R56DK129344-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10412286. Licensed CC0.

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