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Kinetics of human brown adipose tissue activation and deactivation


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.

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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.

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Correspondence to Aaron M. Cypess.

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