Increased brown adipose tissue oxidative capacity in cold-acclimated humans

Abstract

Context: Recent studies examining brown adipose tissue (BAT) metabolism in adult humans have provided convincing evidence of its thermogenic potential and role in clearing circulating glucose and fatty acids under acute mild cold exposure. In contrast, early indications suggest that BAT metabolism is defective in obesity and type 2 diabetes, which may have important pathological and therapeutic implications. Although many mammalian models have demonstrated the phenotypic flexibility of this tissue through chronic cold exposure, little is known about the metabolic plasticity of BAT in humans.

Objective: Our objective was to determine whether 4 weeks of daily cold exposure could increase both the volume of metabolically active BAT and its oxidative capacity.

Design: Six nonacclimated men were exposed to 10°C for 2 hours daily for 4 weeks (5 d/wk), using a liquid-conditioned suit. Using electromyography combined with positron emission tomography with [(11)C]acetate and [(18)F]fluorodeoxyglucose, shivering intensity and BAT oxidative metabolism, glucose uptake, and volume before and after 4 weeks of cold acclimation were examined under controlled acute cold-exposure conditions.

Results: The 4-week acclimation protocol elicited a 45% increase in BAT volume of activity (from 66 ± 30 to 95 ± 28 mL, P < .05) and a 2.2-fold increase in cold-induced total BAT oxidative metabolism (from 0.725 ± 0.300 to 1.591 ± 0.326 mL·s(-1), P < .05). Shivering intensity was not significantly different before compared with after acclimation (2.1% ± 0.7% vs 2.0% ± 0.5% maximal voluntary contraction, respectively). Fractional glucose uptake in BAT increased after acclimation (from 0.035 ± 0.014 to 0.048 ± 0.012 min(-1)), and net glucose uptake also trended toward an increase (from 163 ± 60 to 209 ± 50 nmol·g(-1)·min(-1)).

Conclusions: These findings demonstrate that daily cold exposure not only increases the volume of metabolically active BAT but also increases its oxidative capacity and thus its contribution to cold-induced thermogenesis.

Figure 1.

Study protocol.

Figure 2.

Thermal responses. A, Change in inlet and outlet water temperature of liquid-conditioned garment. B and C, Oxygen consumption (VO₂) (B) and mean skin temperature (C) during room temperature and cold exposure, before and after acclimation. D and E, Shivering intensity (D) and shivering intensity index (E) before and after acclimation. F, Relationship between mean shivering intensity and shivering intensity index (Pearson r = 0.66, P = .02). *, P < .05 vs room temperature, ANOVA with Bonferroni's post hoc test.

Figure 3.

Tissue glucose uptake. A, Coronal view (anterior-posterior projection) of whole-body ¹⁸FDG uptake during cold exposure before and after acclimation. B, Volume of BAT ¹⁸FDG activity before and after acclimation. C, BAT radiodensity by CT during room temperature and cold exposure before and after acclimation. D and E, Fractional (K_i) (D) and net (K_m) (E) glucose uptake in cervicothoracic tissues. F and G, Relationship between BAT radiodensity from CT taken before iv ¹⁸FDG injection in the cold and K_i ¹⁸FDG (Pearson r = 0.71, P = .01) (F) and K_m ¹⁸FDG (Pearson r = 0.72, P = .008) (G). *, P < .05 vs room temperature; $, P < .005 vs BAT; #, P < .05 vs before acclimation, ANOVA with Bonferroni's post hoc test.

Figure 4.

[¹¹C]Acetate kinetics. A–H, ¹¹C time-radioactivity curves over the first 500 seconds of acquisition after [¹¹C]acetate injection at room temperature (red) and during cold exposure (blue) in BAT (A and E), longus colli (B and F), pectoralis (C and G), and cervical sc white adipose tissue (D and H) before and after acclimation. I, Tissue oxidative metabolism index ([¹¹C]acetate k) in cervicothoracic BAT before and after acclimation. J, Total BAT oxidative metabolism index before and after acclimation. *, P < .05 vs room temperature; #, P < .05 vs before acclimation, ANOVA with Bonferroni's post hoc test.