The Importance of Brown Adipose Tissue

Abstract

To the Editor: In the April 9 issue, van Marken Lichtenbelt et al., Cypess et al., and Virtanen et al. report on functioning supraclavicular brown adipose tissue in adult humans. Van Marken Lichtenbelt et al. conclude that brown-adipose-tissue activity induced by exposure to cold is impaired in overweight healthy subjects, and Cypess et al., using epidemiologic-association techniques, conclude that older subjects and those with a higher body-mass index (BMI) have less brown adipose tissue. It is suggested that obesity is associated with reduced brown-adipose-tissue function or activity. However, disseminated brown adipocytes within the large subcutaneous adipose-tissue mass may cumulatively represent substantial brown-adipocyte activity that may not be detected with the use of integrated positron-emission tomography and computed tomography (PET–CT) or crude biochemical studies. Using gene profiling, we found an indication that the brown-adipose-tissue marker uncoupling protein 1 (UCP1) is positively associated with BMI in human subcutaneous adipose tissue (from 33 subjects) (Fig. 1A), as is angiopoietin 2 (ANGP2), a brown-adipose-tissue–enriched angiogenic gene that is a surrogate for F-fluorodeoxyglucose (F-FDG) uptake. Furthermore, cell death–inducing DNA-fragmentation factor (CIDEA), a negative regulator of lipolysis, which is inversely associated with the basal metabolic rate in humans (potentially through indirect UCP1 activation), is reduced in obese subjects matched for glycemic control (Fig. 1B). Such BMI associations are markedly influenced by the presence of diabetes (Fig. 1C and 1D), tempering conclusions about disease drawn from these studies. We have found brown-adipose-tissue markers in obese subjects without diabetes, suggesting that anatomically dispersed brown adipocytes may promote metabolic homeostasis. James A. Timmons, Ph.D.