Identification and importance of brown adipose tissue in adult humans

Abstract

Background: Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans.

Methods: We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery.

Results: Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007).

Conclusions: Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.

2009 Massachusetts Medical Society

Figures

Figure 1. Immunohistochemical Analysis and the Prevalence, Mass, and Activity of Brown Adipose Tissue

Histologic analysis of biopsy specimens from a 48-year-old woman who underwent a parathyroidectomy (Panels A and B) shows the presence of brown adipocytes as stained by either hematoxylin and eosin (Panel A) or antibody to uncoupling protein 1 (UCP1) and counterstained with hematoxylin (Panel B). Panel C shows the quantification of the amount and activity of brown adipose tissue in regions of interest (red outline in images obtained with positron-emission tomography [PET] [left], computed tomography [CT] [center], and combined PET–CT [right]) that included the principal cervical, supraclavicular, and superior mediastinal depots of brown adipose tissue. Panel D shows the prevalence of detectable brown adipose tissue in men and women. Panel E shows the mass of brown adipose tissue in grams and Panel F the activity of brown adipose tissue in grams times the mean standardized uptake value (SUV) in grams per milliliter. In Panels E and F, the box plots indicate the lower quartile (lower line), median quartile (middle line), upper quartile (upper line), 1.5 times the interquartile range (lower and upper whiskers), and outliers (circles).

Figure 2. Correlation between the Prevalence of Maximal Activity of Brown Adipose Tissue and Temperature, Age, Body-Mass Index, and Glucose Level

In Panel A, for the patients with detectable brown adipose tissue, the dates on which the activity of the tissue was maximal were determined. The prevalence of maximal activity of brown adipose tissue is plotted against the mean monthly outdoor temperature in Boston after adjustment for age and sex in multivariate logistic regression. The prevalence of maximal activity of brown adipose tissue when data for men and women were combined decreased with increasing mean outdoor temperature (P = 0.02). At every temperature, the probability of the detection of maximal brown adipose tissue was significantly higher for women than for men (P