Relationship Between Brown Adipose Tissue and Shivering in Cold‐Exposed Humans

Abstract

Background An inverse relationship between brown adipose tissue (BAT) volume and shivering intensity has previously been reported in humans. Considering its small volume in adult humans, this inverse relationship may be explained by the regional distribution of BAT. It has been postulated that the paraspinal depot may be critical to heating the spinal cord to maintain neural conductivity under cold stimulation. However, this local heating may also suppress the drive to shiver, a phenomenon previously shown in guinea pigs. Objective The research objective was to determine whether the presence of paraspinal BAT can modulate the intensity and pattern of shivering in lean, healthy, adult humans. Hypothesis We propose that paraspinal BAT thermogenesis can supress shivering intensity and modulate the shivering pattern. Methodology The present data includes 23 young women who completed a 3h mild cold exposure protocol, using a liquid-conditioned suit perfused with water at 18°C. During cold exposure, participants remained supine in a PET/CT scanner. An i.v. bolus of [11C]-acetate and [18F]FDG were given sequentially, with each injection followed by a 30 min list-mode dynamic PET acquisition to quantify depot-specific BAT oxidative metabolism and glucose uptake, respectively. Finally, a whole-body static PET acquisition was performed to quantify the total BAT volume and distribution. Surface electromyography (sEMG) was used to characterize shivering activity in 8 different muscles. Shivering intensity and shivering pattern were determined using custom-designed EMG algorithms. In brief, the two distinct shivering patterns (continuous vs burst shivering) are distinguished according to differences in frequency of occurrence (4-8 Hz for continuous vs. 0.1-0.2 Hz for bursts) and intensity [2-5% maximal voluntary contraction (MVC) for continuous vs. 7-15% MVC for bursts]. Results Total BAT volume was estimated at 53 mL (95% CI: 34 to 72 mL) with paraspinal BAT volume accounting for 9% (95% CI: 5 to 13%) of total BAT. Mean shivering intensity under this cold stimulus was 3.0 % MVC (95% CI: 2.0 to 3.8 %). Shivering bursts occurred at a frequency of 2.8 bursts/min (95% CI: 2.3 to 3.2 bursts/min), eliciting a shivering intensity of 9.6 % MVC (95% CI: 5.9 to 13.3 % MVC), while the more continuous low-intensity shivering was maintained at 3.0 % MVC (95% CI: 1.6 to 4.4% MVC). Pearson correlations revealed no associations between total BAT volume, shivering intensity or shivering pattern. Similarly, paraspinal BAT volume was not associated with any shivering outcomes. Conclusion The role of BAT in humans is still not clearly elucidated. Here we showed that in premenopausal women, neither total BAT volume nor paraspinal BAT are associated with shivering intensity or shivering pattern. Further studies are required to determine whether BAT plays a more regionalized role, unique to each depot, or more globally on whole-body energy metabolism.