Identification and Importance of Brown Adipose Tissue in Adult Humans
Aaron M. Cypess, M.D., Ph.D., M.M.Sc., Sanaz Lehman, M.B., B.S., Gethin Williams, M.B., B.S., Ph.D., Ilan Tal, Ph.D., Dean Rodman, M.D., Allison B. Goldfine, M.D., Frank C. Kuo, M.D., Ph.D., Edwin L. Palmer, M.D., Yu-Hua Tseng, Ph.D., Alessandro Doria, M.D., Ph.D., M.P.H., Gerald M. Kolodny, M.D., and C. Ronald Kahn, M.D.
Background Obesity results from an imbalance between energyintake and expenditure. In rodents and newborn humans, brownadipose tissue helps regulate energy expenditure by thermogenesismediated by the expression of uncoupling protein 1 (UCP1), butbrown adipose tissue has been considered to have no physiologicrelevance in adult humans.
Methods We analyzed 3640 consecutive 18F-fluorodeoxyglucose(18F-FDG) positron-emission tomographic and computed tomographic(PET–CT) scans performed for various diagnostic reasonsin 1972 patients for the presence of substantial depots of putativebrown adipose tissue. Such depots were defined as collectionsof tissue that were more than 4 mm in diameter, had the densityof adipose tissue according to CT, and had maximal standardizeduptake values of 18F-FDG of at least 2.0 g per milliliter, indicatinghigh metabolic activity. Clinical indexes were recorded andcompared with those of date-matched controls. Immunostainingfor UCP1 was performed on biopsy specimens from the neck andsupraclavicular regions in patients undergoing surgery.
Results Substantial depots of brown adipose tissue were identifiedby PET–CT in a region extending from the anterior neckto the thorax. Tissue from this region had UCP1-immunopositive,multilocular adipocytes indicating brown adipose tissue. Positivescans 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 adiposetissue and higher 18F-FDG uptake activity. The probability ofthe detection of brown adipose tissue was inversely correlatedwith years of age (P<0.001), outdoor temperature at the timeof the scan (P=0.02), beta-blocker use (P<0.001), and amongolder patients, body-mass index (P=0.007).
Conclusions Defined regions of functionally active brown adiposetissue are present in adult humans, are more frequent in womenthan in men, and may be quantified noninvasively with the useof 18F-FDG PET–CT. Most important, the amount of brownadipose tissue is inversely correlated with body-mass index,especially in older people, suggesting a potential role of brownadipose tissue in adult human metabolism.
Source Information
From the Research Division, Joslin Diabetes Center (A.M.C., A.B.G., Y.-H.T., A.D., C.R.K.); the Division of Nuclear Medicine, Beth Israel Deaconess Medical Center (S.L., G.W., I.T., D.R., G.M.K.); the Department of Pathology, Brigham and Women's Hospital (F.C.K.); the Division of Nuclear Medicine, Massachusetts General Hospital (E.L.P.); and Harvard Medical School (A.M.C., S.L., G.W., I.T. D.R., A.B.G., F.C.K., E.L.P., Y.-H.T., A.D., G.M.K., C.R.K.) — all in Boston.
Address reprint requests to Dr. Kahn at the Section on Obesity and Hormone Action, Joslin Diabetes Center, 1 Joslin Pl., Boston, MA 02215, or at c.ronald.kahn{at}joslin.harvard.edu.
The Importance of Brown Adipose Tissue
Timmons J. A., Pedersen B. K., Stefan N., Pfannenberg C., Häring H.-U., Villarroya F., Domingo P., Giralt M., Jacene H. A., Wahl R. L., Lee P., Ho K. K.Y., Fulham M. J., Sacks H. S., van Marken Lichtenbelt W. D., Schrauwen P., Teule G.J. J., Cypess A. M., Kahn C. R., Enerbäck S., Oksi J., Nuutila P.
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N Engl J Med 2009;
361:415-421, Jul 23, 2009.
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