Stimulation of the beta-2-adrenergic receptor with salbutamol activates human brown adipose tissue

While brown adipose tissue (BAT) is activated by the beta-3-adrenergic receptor (ADRB3) in rodents, in human brown adipocytes, the ADRB2 is dominantly present and responsible for noradrenergic activation. Therefore, we performed a randomized double-blinded crossover trial in young lean men to compare the effects of single intravenous bolus of the ADRB2 agonist salbutamol without and with the ADRB1/2 antagonist propranolol on glucose uptake by BAT, assessed by dynamic 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan (i.e., primary outcome). Salbutamol, compared with salbutamol with propranolol, increases glucose uptake by BAT, without affecting the glucose uptake by skeletal muscle and white adipose tissue. The salbutamol-induced glucose uptake by BAT positively associates with the increase in energy expenditure. Notably, participants with high salbutamol-induced glucose uptake by BAT have lower body fat mass, waist-hip ratio, and serum LDL-cholesterol concentration. In conclusion, specific ADRB2 agonism activates human BAT, which warrants investigation of ADRB2 activation in long-term studies (EudraCT: 2020-004059-34). [Display omitted] •ADRB2 agonism by salbutamol increases glucose uptake by human BAT in vivo•ADRB2 agonism increases energy expenditure correlating with BAT glucose uptake•ADRB2 agonism does not increase glucose uptake by skeletal muscle and WAT•ADRB1/2 antagonism blocks salbutamol-induced glucose uptake by human BAT Brown adipose tissue (BAT) activation is an attractive strategy to improve cardiometabolic health. While ADRB3 is responsible for BAT activation in rodents, the ADRB2 predominates on human brown adipocytes. Straat et al. reveal that ADRB2 agonism by salbutamol increases glucose uptake by human BAT and energy expenditure in vivo.