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Cold-Activated Brown Adipose Tissue in Healthy Men

sponse to cold exposure, with lean subjects hav- ing an increase of 0.13±0.16°C (P =0.06 for the comparison with body), and obese or overweight subjects an increase of 0.16±0.22°C (P=0.02). The mean skin temperature dropped significantly in both study groups, by 3.4±0.9°C in the lean sub- jects and by 3.7±0.5°C in the overweight or obese subjects. The core skin temperature gradient in- creased significantly during cold exposure as compared with the gradient under thermoneutral conditions (P<0.001) (Table 2). The underarm– fingertip gradient also increased during cold ex- posure, indicating vasoconstriction in the skin of the extremities.21 The resting metabolic rate adjusted for fat-free mass was 8.46±0.93 MJ per 24 hours in the lean subjects and 8.16±0.29 MJ per 24 hours in the overweight or obese subjects. The rate increased significantly during exposure to cold in both groups (P<0.001 for both com- parisons) (Table 2), with much individual varia- tion, ranging from 5 to 30%. No shivering was reported.



Nonlinear regression analysis showed that the activity of whole-body brown adipose tissue was negatively correlated with BMI (r=−0.60, P=0.002) and percentage of body fat (r=−0.60, P=0.001) (Fig. 3A and 3B). There was no correlation be- tween brown-adipose-tissue activity and age, and in a stepwise regression analysis, BMI but not age was significantly associated with brown-adipose- tissue activity.


Brown Adipose Tissue

White Adipose Tissue

Brown Adipose Tissue

White Adipose Tissue

Brown Adipose Tissue

White Adipose Tissue

The change in distal temperature from thermo- neutral conditions to cold exposure was related to brown-adipose-tissue activity (r=0.41, P=0.04), suggesting that a higher level of activity is associ- ated with a smaller decrease in mean skin tem- perature and that brown-adipose-tissue activity may contribute to the regulation of body tempera- ture by increasing the production of body heat. However, we did not find a significant relation between cold-induced thermogenesis and brown- adipose-tissue activity. The resting metabolic rate was positively correlated with brown-adipose-tissue activity both under thermoneutral conditions (r= 0.56, P=0.005; with one outlier removed, r=0.64, P=0.001) (Fig. 4) and during cold exposure (r=0.40, P=0.05; with the same outlier removed, r=0.46, P=0.03), indicating that brown-adipose- tissue activity is involved in energy metabolism. The core temperature under thermoneutral condi- tions was also positively correlated with brown- adipose-tissue activity (r=0.48, P=0.03).

Figure 2. Specimens of Brown and White Adipose Tissue from the Supra- clavicular Region in a 46-Year-Old Woman.

Specimens stained with hematoxylin and eosin (Panel A) show granular cyto­ plasm containing mitochondria and multiple fat vacuoles, which are charac­ teristic of brown adipose tissue, and a single large lipid vacuole in each white fat cell. The use of immunofluorescence assay for an antibody to uncoupling protein 1 (UCP1) together with the nuclei­staining dye 4,6­diamidino­2­ phenylindole (Panel B) shows positive immunostaining for UCP1 (green) in brown adipose tissue but not in white adipose tissue. Control specimens were stained with 4,6­diamidino­2­phenylindole in phosphate­buffered saline (Panel C).


We observed a very high rate of occurrence of brown adipose tissue in normal young men (>95%). In tissue samples taken from the supraclavicular area of a surgical patient, an immunofluores- cence assay revealed the presence of UCP1, con- firming the presence of brown adipose tissue

n engl j med 360;15


april 9, 2009


The New England Journal of Medicine Downloaded from nejm.org on February 3, 2015. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved.

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