Cold-Activated Brown Adipose Tissue in Healthy Men
to cold temperatures. Thus, subjects with the highest level of brown-adipose-tissue activity had the lowest drop in distal temperature, suggesting that these subjects were able to maintain core body temperature through an increase in body heat. However, contrary to our expectation, there was no significant relation between brown-adi- pose-tissue activity and cold-induced thermogen- esis. The most likely reason is that other tissues, such as skeletal muscle,1 may be involved in the thermogenic response. Indeed, we recently found that mitochondrial uncoupling in skeletal mus- cle is significantly related to cold-induced adap- tive thermogenesis in humans.24 Given the find- ings of an earlier study, in which subjects were exposed to cold for 1 hour,2 we expected less cold-induced thermogenesis in the group of over- weight or obese subjects than in the lean group, but the groups did not differ significantly in this respect. Even though the overweight or obese sub- jects had an increase in thermogenesis on expo- sure to cold that was similar to the increase in the lean subjects, they had less brown-adipose- tissue activity (or none).
Recent studies conducted at the molecular level have identified a mechanism by which PR domain containing 16 (PRDM16), a zinc-finger protein selectively expressed in brown adipose tissue, can induce gene expression in brown adi- pose tissue while suppressing it in white adipose tissue, thereby controlling the induction of brown
Moreover, there is recent evi-
dence that brown adipose tissue is more closely related to skeletal muscle than to white adipose
Energy Expenditure (MJ/24 hr)
600 BAT Activity (kBq)
Figure 4. Resting Metabolic Rate in Relation to Brown-Adipose-Tissue Activity.
Resting metabolic rate, adjusted for fatfree mass at thermoneutral condi tions, is shown in relation to brownadiposetissue (BAT) activity. (With the exclusion of one outlier, indicated by a triangle, r=0.64 and P =0.001.)
of brown-adipose-tissue activity in young men is related to energy metabolism. Further work is needed to understand brown-adipose-tissue activ- ity in relation to skeletal-muscle metabolism; ideally, this work will be conducted along with molecular studies that may delineate the relative contribution of each to adaptive thermogenesis.
tissue.27,28 A putative shared lineage between brown adipose tissue and skeletal muscle may provide clues about the origins of stem cells that lead to the formation of brown fat and to adap- tive thermogenesis.
Our study suggests that the relatively high level
No potential conflict of interest relevant to this article was reported.
We thank Loek Wouters, Paul Schoffelen, and Emiel Beijer for their technical support; David Creytens and Gert Schaart for the analyses of biopsy specimens; and the members of our Tempera- ture Literature Club, especially Sander Wijers, for helpful sug- gestions.
1. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature 2000;404:652-60. 2. Claessens-van Ooijen AM, Westerterp KR, Wouters L, Schoffelen PF, van Steen- hoven AA, van Marken Lichtenbelt WD. Heat production and body temperature during cooling and rewarming in over- weight and lean men. Obesity (Silver Spring) 2006;14:1914-20. 3. Christiansen E, Garby L. Prediction of body weight changes caused by changes
in energy balance. Eur J Clin Invest 2002; 32:826-30. 4. Ravussin E, Lillioja S, Knowler WC, et al. Reduced rate of energy expenditure as a risk factor of body weight gain. N Engl J Med 1988;318:467-72. 5. Griffiths M, Payne PR, Stunkard AJ, Rivers JPW, Cox M. Metabolic rate and physical development in children at risk of obesity. Lancet 1990;336:76-8. 6. Wijers SLJ, Saris WHM, van Marken Lichtenbelt WD. Individual thermogenic
responses to mild cold and overfeeding are closely related. J Clin Endocrinol Me- tab 2007;92:4299-305. 7. Huttunen P, Hirvonen J, Kinnula V. The occurrence of brown adipose tissue in outdoor workers. Eur J Appl Physiol Oc- cup Physiol 1981;46:339-45. 8. Heaton JM. The distribution of brown adipose tissue in the human. J Anat 1972; 112:35-9. 9. Astrup A, Bulow J, Madsen J, Chris- tensen NJ. Contribution of BAT and skel-
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