Brown adipose tissue (BAT) has been identified as a potential target in the treatment and prevention of obesity and metabolic disease. The precise kinetics of BAT activation and the duration of stimulus required to recruit metabolically active BAT, and its subsequent deactivation, are not well-understood. In this clinical trial, 19 healthy adults (BMI: 23.7 ± 0.7 kg/m2, Age: 31.2 ± 2.8 year, 12 female) underwent three different cooling procedures to stimulate BAT glucose uptake, and active BAT volume was determined using 18F-Fluorodeoxyglucose (FDG) PET/CT imaging. We found that 20 min of pre-injection cooling produces activation similar to the standard 60 min (39.9 mL vs. 44.2 mL, p = 0.52), indicating that BAT activity approaches its peak function soon after the initiation of cooling. Furthermore, upon removal of cold exposure, active BAT volume declines (13.6 mL vs. 44.2 mL, p = 0.002), but the deactivation process persists even hours following cessation of cooling. Thus, the kinetics of human BAT thermogenesis are characterized by a rapid increase soon after cold stimulation but a more gradual decline after rewarming. These characteristics reinforce the feasibility of developing mild, short-duration cold exposure to activate BAT and treat obesity and metabolic disease.
This is a preview of subscription content, access via your institution
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Collaborators TG 2015 O. Health effects of overweight and obesity in 195 countries over 25 years. New Engl J Med. 2017;377:13–27.
Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309:71–82.
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. New Engl J Med. 2009;360:1509–17.
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JMAFL, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. New Engl J Med. 2009;360:1500–8.
Brendle C, Werner MK, Schmadl M, la Fougère C, Nikolaou K, Stefan N, et al. Correlation of brown adipose tissue with other body fat compartments and patient characteristics: a retrospective analysis in a large patient cohort using PET/CT. Acad Radiol. 2017. https://doi.org/10.1016/j.acra.2017.09.007.
Matsushita M, Yoneshiro T, Aita S, Kameya T, Sugie H, Saito M. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes. 2014;38:812–7.
Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011;14:272–9.
Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98:E1218–23.
Ouellet V, Labbé SM, Blondin DP, Phoenix S, Guérin B, Haman F, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Investig. 2012;122:545–52.
Hanssen MJW, Hoeks J, Brans B, van der Lans AAJJ, Schaart G, van den Driessche JJ, et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med. 2015;21:863–5.
Lans AAJJ, van der, Wierts R, Vosselman MJ, Schrauwen P, Brans B, et al. Cold-activated brown adipose tissue in human adults: methodological issues. Am J Physiol Regul Integr Comp Physiol. 2014;307:R103–13.
Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA, et al. Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab. 2016;24:210–22.
Sylow L, Kleinert M, Richter EA, Jensen TE. Exercise-stimulated glucose uptake—regulation and implications for glycaemic control. Nat Rev Endocrinol. 2017;13:133–48.
Zaretskaia MV, Zaretsky DV, Shekhar A, DiMicco JA. Chemical stimulation of the dorsomedial hypothalamus evokes non-shivering thermogenesis in anesthetized rats. Brain Res. 2002;928:113–25.
Hany TF, Gharehpapagh E, Kamel EM, Buck A, Himms-Hagen J, von Schulthess GK. Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med. 2002;29:1393–8.
Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in Supraclavicular Area Fat (“USA-Fat”): description on 18F-FDG PET/CT. J Nucl Med. 2003;44:170–6.
Cypess AM, Chen Y-C, Sze C, Wang K, English J, Chan O, et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci USA. 2012;109:10001–5.
Leitner BP, Huang S, Brychta RJ, Duckworth CJ, Baskin AS, McGehee S, et al. Mapping of human brown adipose tissue in lean and obese young men. PNAS. 2017: 201705287.
AMJC Ooijen, Westerterp KR, Wouters L, Schoffelen PFM, van Steenhoven AA, van Lichtenbelt WDM. Heat production and body temperature during cooling and rewarming in overweight and lean men. Obesity. 2006;14:1914–20.
Haman F, Mantha OL, Cheung SS, DuCharme MB, Taber M, Blondin DP, et al. Oxidative fuel selection and shivering thermogenesis during a 12- and 24-h cold-survival simulation. J Appl Physiol. 2016;120:640–8.
Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang A-H, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150:366–76.
Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic Peroxisome Proliferator-activated Receptor γ (PPARγ) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285:7153–64.
Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, et al. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell. 2015;163:643–55.
Blondin DP, Labbé SM, Tingelstad HC, Noll C, Kunach M, Phoenix S, et al. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab. 2014;99:E438–46.
We thank the Beth Israel Deaconess Medical Center (BIDMC) Clinical Research Center nursing team, Bionutrition Core, research pharmacy, and nuclear medicine technologists for the excellent support they provided; C. Ronald Kahn for his advice in experimental design; Esti Anflick-Chames for her thoughts on data analysis; and our volunteers for their commitment to the studies. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), DK075112 and DK075116; National Institutes of Health (NIH) Grants DK081604 and DK046200 (to AMC); RR025757; Grant P30 DK036836 from the NIDDK; Clinical Translational Science Award UL1RR025758 to Harvard University and the BIDMC from the National Center for Research Resources, Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH Award UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers); and the Eli Lilly Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Leitner, B.P., Weiner, L.S., Desir, M. et al. Kinetics of human brown adipose tissue activation and deactivation. Int J Obes 43, 633–637 (2019). https://doi.org/10.1038/s41366-018-0104-3