Abstract

BackgroundHuman brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT.Methods and FindingsFifteen patients with stable VNS therapy (age: 45±10yrs; body mass index; 25.2±3.5 kg/m2) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUVMean; 0.55±0.25 versus 0.67±0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001).ConclusionsVNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy.Trial RegistrationThe study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

Highlights

  • Obesity results from an imbalance between energy intake and energy expenditure and most applied obesity therapies are focussed on decreasing energy intake. [1]

  • The observed change in energy expenditure was significantly related to the change in brown adipose tissue (BAT) activity

  • This suggests a role for BAT in the Vagus nerve stimulation (VNS) increase in energy expenditure

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Summary

Introduction

Obesity results from an imbalance between energy intake and energy expenditure and most applied obesity therapies are focussed on decreasing energy intake. [1]. In addition to a reduction in energy intake, increasing energy expenditure could be an effective means to prevent or treat obesity. In rodents, activated brown adipose tissue (BAT) is the main contributor to the regulated energy expenditure. During cold exposure BAT activation increases energy expenditure by producing heat (thermogenesis) to prevent hypothermia. Functional brown adipose tissue (BAT) was shown in adult man by means of FDG-PET-CT (18F-fluorodeoxyglucose positron-emission tomography and computed tomography). BAT activity was inversely correlated with body mass index (BMI) and body fat percentage (BF%) [3,5]. Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. We hypothesize VNS increases energy expenditure by activating BAT

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