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Vagus nerve stimulation increases energy expenditure

at least part of the effect of VNS intervention on energy expenditure can be explained by BAT activity
Short-term interruption of VNS therapy by turning off the VNS for only several hours significantly decreased energy expenditure

Vagus nerve stimulation (VNS) is accompanied by an increase in whole body energy expenditure and this thermogenesis is related to changes in brown adipose tissue (BAT) activity, according to a study publishing online 'Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity', in the journal PLoS ONE.

It is known that human 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. VNS is used for refractory epilepsy, but has been reported to reported to generate weight loss.

The study researchers from Maastricht University Medical Center, Maastricht, The Netherlands, sought to define the relation between VNS energy expenditure and BAT activation in a patient cohort on chronic stable VNS therapy for refractory epilepsy, and hypothesised that VNS increases energy expenditure by stimulating BAT activity.


Between January 2011 and June 2012 ,15 patients on stable VNS therapy using the Vagus Nerve Stimulation Therapy System (VNS Therapy, Cyberonics) for refractory epilepsy were recruited for the study.

Energy expenditure was measured using indirect calorimetry and BAT activity was assessed by means of FDG-PET-CT during actual VNS and when VNS was inactivated. In addition, they compared BAT activity during VNS and during mild cold stimulation. The mild cold intervention served as a control since it is known to activate BAT.

Ten patients were measured in thermoneutral (TN) conditions with active (VNS-On) and inactive VNS (VNS-Off) respectively. In addition, five subjects were measured with active VNS in TN conditions (VNS-TN) and during mild cold exposure (VNS-Cold) respectively.

Subjects were measured under fasted conditions (no food intake from 10pm the night before, only water consumption was allowed) from 9am to 2pm under supervision of a specialized research nurse. VNS-On and VNS-Off took place on separate occasions within 14 days. During VNS-Off the system was inactivated (output current 0 mA, magnet function 0 mA) at 9:30am prior to the measurements. At the end of the test day (2:00pm) the VNS system was re-activated. During VNS-Cold the settings of the VNS system were not adjusted. VNS-TN and VNS-Cold were also performed within a 14-day period. Body composition (body fat%, fat mass (FM), fat free mass (FFM)) was determined by dual x-ray absorptiometry (DXA, type Discovery A, Hologic, Bedford, MA, USA).

Ten male and five female patients with a mean age of 45±10 years and a mean BMI of 25.2±3.5 that were (successfully) treated with VNS for refractory epilepsy were included (Table 2). VNS implantation was on average 59±19 months (range; 22–89 months) ago and all subjects did not have any recent adjustments in their VNS settings or medication.

Pre-VNS treatment body weight and BMI were retraceable for 11 subjects and were not significantly different from weight and BMI during the study (implant weight and BMI; 71.2±12.5, 24.7±3.4, current weight and BMI; 72.9±11.6, 25.2±3.5, p=0.414). The subject characteristics were not different for the On/Off (n = 10) versus the TN/Cold group (n = 5) (Table 1).

Table 1. Subject characteristics for all subjects, the intervention group with Vagus Nerve Stimulator (VNS) On and Off (n = 10) and for the group with VNS during thermoneutral (VNS-TN) conditions and cold exposure (VNS-Cold) (n = 5).


The researchers report that basal metabolic rate (BMR) decreased significantly when VNS was turned off (68.6±7.9 J/s versus 67.2±8.1 J/s, p=0.038, mean change; 2.2%, range; −3.1 to 7.8%, Figure 1).

Figure 1. Basal metabolic rate (BMR) during active and inactive VNS in relation to BAT activity.

Figure 2 shows representative images of FDG-uptake on PET-CT in the studied groups. The mean SUV for BAT showed no statistical difference during VNS (BAT SUVMean; 0.55±0.25 versus 0.67±0.46, p=0.619). In different muscles analysed, the triceps muscle had a significantly increased FDG-uptake when VNS was turned off. However, for all muscles together there was no significant change in activity.

Figure 2: FDG-PET-CT images of intervention group and cold exposed subjects.

After cold exposure, all subjects showed increased BAT activity (BAT SUVMean; 0.65±0.29 versus 3.40±1.63, p=0.012).

Figure 3. FDG-PET-CT activity of different tissue types upon VNS intervention.

Energy expenditure during VNS-On and VNS-Off measurements was not related to BAT activity, activity of other tissue (Muscle, WAT), skin perfusion, core and skin temperatures or any other study parameter in either uni- or multivariate analyses. However, the change in energy expenditure upon VNS intervention (from VNS-On to VNS-Off) was positively correlated to the change in BAT activity (exponential curve fitting, r = 0.935, p<0.001).

“This study shows that even short-term interruption of VNS therapy by turning off the VNS for only several hours significantly decreased energy expenditure in a cohort of treatment-stable VNS patients,” the authors note. “Despite the fact that mean BAT activity did not increase upon VNS, the change in BAT activity explained a significant part of the change in energy expenditure. To our opinion, this suggests at least part of the effect of VNS intervention on energy expenditure can be explained by BAT activity.”

The study was registered in the Clinical Trial Register under the Identifier NCT01491282.

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