Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity

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.

Role of the autonomic nervous system in activation of human brown adipose tissue: A review of the literature

“…While no significant difference in BAT activity was found between active and inactive VNS therapy, the change in energy expenditure after inactivation of VNS was significantly related to changes in BAT activity [70]. Nevertheless, it should be noted that the patients in this study were relatively old for the detection of active BAT, as BAT activity is known to diminish with increasing age [2].…”

Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway

“…Other methods of electrical stimulation, such as gastrointestinal stimulation and vagal nerve stimulation, have also been reported for the treatment of obesity and diabetes [20][21][22][23][24][25][26]. Gastric electrical stimulation (GES) was reported to reduce food intake and body weight in animal and human studies [20][21][22][23].…”

“…GES performed by implanting the Tantalus system was reported to be a safe and effective treatment of type 2 diabetes mellitus by reducing other cardiometabolical risky factors [24]. Vagal nerve stimulation was reported to increases energy expenditure relating to brown adipose tissue activity [25] and to decrease body mass index (BMI) [26]. One common problem with these electrical stimulation therapies is the lack of controlled data.…”

Immunity-Based Evolutionary Interpretation of Diet-Induced Thermogenesis

“…Moreover, a causal relationship between vagal afferent activation and energy expenditure increase has been demonstrated under different conditions. For example, vagal stimulation applied to manage human refractory epilepsy was found to induce BAT activity and energy expenditure (Vijgen et al, 2013). Vagal afferents also play a key role in mediating local gut interleukin-1-induced fever (Hansen et al, 2001).…”