Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity

Guy H E J Vijgen, Nicole D Bouvy, Loes Leenen, Kim Rijkers, Erwin Cornips, Marian Majoie, Boudewijn Brans, Wouter D van Marken Lichtenbelt, Guy H E J Vijgen, Nicole D Bouvy, Loes Leenen, Kim Rijkers, Erwin Cornips, Marian Majoie, Boudewijn Brans, Wouter D van Marken Lichtenbelt

Abstract

Background: Human 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 findings: Fifteen patients with stable vns therapy (age: 45 ± 10 yrs; body mass index; 25.2 ± 3.5 kg/m(2)) 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 SUV(Mean); 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).

Conclusions: VNS 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 registration: The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Basal metabolic rate (BMR) during…
Figure 1. Basal metabolic rate (BMR) during active and inactive VNS in relation to BAT activity.
A. Individual responses upon VNS intervention. Notice all but one (marked line) subjects decreased energy expenditure upon deactivation of the VNS (subject that increased energy expenditure also described in Results section). B. Mean group BMR upon VNS intervention. C. The change in energy expenditure (Δ Energy Expenditure) upon VNS intervention (On/Off) correlated to the change in BAT activity. One subject (open dot) showed a high increase in energy expenditure upon VNS intervention. This subject was confirmed as an statistical outlier in the exponential growth equation shown and therefore excluded from the equation. Values shown are means + S.E.M. Significance shown for paired t-test in VNS intervention group consisting of 4 males and six females. * P<0.05
Figure 2. FDG-PET-CT images of intervention group…
Figure 2. FDG-PET-CT images of intervention group and cold exposed subjects.
Transaxial and coronal CT, PET and PET-CT fused images of VNS-On and VNS-Off from a subject in the VNS-On/Off group and images from a subject in the VNS-TN/Cold group during thermoneutral conditions (TN) and cold exposure (Cold). PET-CT image shown with and without Volume-Of-Interest (VOI) cubes for determination of activity. The white line in the coronal image indicates the transaxial slice shown above.
Figure 3. FDG-PET-CT activity of different tissue…
Figure 3. FDG-PET-CT activity of different tissue types upon VNS intervention.
SUVMean values for Brown Adipose Tissue (BAT), all muscle (Muscle), deltoid muscle (Deltoid), biceps muscle (Biceps), triceps muscle (Triceps), erector spinae muscle at the level of vertebrae C7 (C7), T8 (T8), L3 (L3), subcutaneous white adipose tissue (WAT Sc), visceral white adipose tissue (WAT Visc), the liver (Liver) and the brain at the level of the cerebellum (Brain). A. Comparison of activity during VNS-On and VNS-Off. B. Comparison of activity between VNS-On, VNS-Off and VNS-Cold. Values shown are mean + S.E.M. * P<0.05 for paired t-tests between VNS-On and VNS-Off. # P<0.05 for one-way ANOVA with post-hoc Bonferroni correction between VNS-On, VNS-Off and VNS-Cold.

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