Deep Brain Stimulation of the Hypothalamus Leads to Increased Metabolic Rate in Refractory Obesity

Abstract

Objective: Obesity has become a worldwide epidemic, with very few long-term successful treatment options for refractory disease. Deep brain stimulation (DBS) of the bilateral lateral hypothalamus (LH) in refractory obesity has been performed safely. However, questions remain regarding the optimal settings and its effects on metabolic rate. The goals of our experiment were to determine the optimal DBS settings and the actual effect of optimal stimulation on energy expenditure.

Methods: After bilateral LH DBS implantation, 2 subjects with treatment refractory obesity underwent 4 days of metabolic testing. The subjects slept overnight in a respiratory chamber to measure their baseline sleep energy expenditure, followed by 4 consecutive days of resting metabolic rate (RMR) testing at different stimulation settings. On day 4, the optimized DBS settings were used, and sleep energy expenditure was measured again overnight in the room calorimeter.

Results: During daily testing, the RMR fluctuated acutely with changes in stimulation settings and returned to baseline immediately after turning off the stimulation. Optimal stimulation settings selected for participants showed a 20% and 16% increase in RMR for the 2 participants. Overnight sleep energy expenditure measurements at these optimized settings on day 4 yielded a 10.4% and 4.8% increase over the baseline measurements for the 2 participants.

Conclusions: These findings have demonstrated the efficacy of optimized DBS of the LH on increasing the RMR acutely and maintaining this increase during overnight sleep. These promising preliminary findings have laid the groundwork for the possible treatment of refractory obesity with DBS.

Keywords: Deep brain stimulation; Functional neurosurgery; Lateral hypothalamus; Neuromodulation; Obesity.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Study design. DXA, bone dual-energy x-ray absorptiometry; RMR, resting metabolic rate.

Figure 2.

Example day of optimal stimulation search testing (mean resting metabolic rate [RMR] for baseline, stimulation interval, and once stimulation was turned off) for (A) participant 1 and (B) participant 2. Setting 9 for participant 1 on day 2 could not be used because of patient movement at testing.

Figure 3.

Sleep energy expenditure (kcal/24 hours) without stimulation and at the “optimal” stimulation setting.