Background: Brown adipose tissue (BAT) contributes significantly to energy expenditure in adult humans. It is regulated by the sympathetic nervous system via β-adrenergic receptors (β-ARs). The predominant β-ARs in human BAT are β1 and β2. Selective β2-AR agonists may offer a way of harnessing BAT to combat obesity without β1 cardiac effects.
Aim: To investigate whether formoterol, a highly selective β2-adrenergic agonist, activates BAT.
Method: In a randomised double-blind cross-over design, 10 healthy young adults (BMI mean±SEM 24±1kg/m2) underwent 1 week each of oral formoterol (80mcg/day) and placebo treatments with an intervening 2-week wash-out. After each treatment, under standardised cooling (190C), BAT function was assessed by measuring (i) BAT activity by FDG-PET-CT (ii) supraclavicular (SCL) skin temperatures by infrared thermography (iii) energy production after a standardised meal using indirect calorimetry. Blood glucose, free fatty acid (FFA) and formoterol concentrations were measured.
Results: Formoterol treatment achieved plasma drug concentration of 59±12pg/mL. BAT FDG uptake was not significantly different between formoterol and placebo treatments. Mean SCL temperature fell during cooling and rose after the meal by similar degrees with both treatments. Resting metabolic rate (RMR) was significantly higher during formoterol treatment. Energy production was stimulated by the meal, an effect which was significantly lower during formoterol treatment. Fasting plasma glucose (4.6±0.1 vs 5.4±0.1mmol/L, P<0.01) and FFA (0.36±0.08 vs 0.49±0.06mmol/L, P=0.025) concentrations were higher during formoterol treatment.
Summary: Formoterol did not change BAT function on PET-CT nor affect thermogenesis. Formoterol increased RMR but reduced energy production after a meal.
Conclusion: β2-AR does not regulate BAT function in humans. The metabolic effects of β2-AR agonist are not BAT mediated.
Acknowledgement: M Thuzar is supported by the Princess Alexandra Hospital Research Support Scheme. Formoterol was supplied by Shou Chan Co., Ltd, Taiwan.