Effect of β1- and β2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans

In humans, beta-adrenergic stimulation increases energy and fat metabolism. In the case of beta(1)-adrenergic stimulation, it is fueled by an increased lipolysis. We examined the effect of beta(2)-adrenergic stimulation, with and without a blocker of lipolysis, on thermogenesis and substrate oxidation. Furthermore, the effect of beta(1)- and beta(2)-adrenergic stimulation on uncoupling protein 3 (UCP3) mRNA expression was studied. Nine lean males received a 3-h infusion of dobutamine (DOB, beta(1)) or salbutamol (SAL, beta(2)). Also, we combined SAL with acipimox to block lipolysis (SAL + ACI). Energy and substrate metabolism were measured continuously, blood was sampled every 30 min, and muscle biopsies were taken before and after infusion. Energy expenditure significantly increased similar to13% in all conditions. Fat oxidation increased 47 +/- 7% in the DOB group and 19 +/- 7% in the SAL group but remained unchanged in the SAL + ACI condition. Glucose oxidation decreased 40 +/- 9% upon DOB, remained unchanged during SAL, and increased 27 +/- 11% upon SAL + ACI. Plasma free fatty acid (FFA) levels were increased by SAL ( 57 +/- 11%) and DOB ( 47 +/- 16%), whereas SAL + ACI caused about fourfold lower FFA levels compared with basal levels. No change in UCP3 was found after DOB or SAL, whereas SAL + ACI downregulated skeletal muscle UCP3 mRNA levels 38 +/- 13%. In conclusion, beta(2)-adrenergic stimulation directly increased energy expenditure independently of plasma FFA levels. Furthermore, this is the first study to demonstrate a downregulation of skeletal muscle UCP3 mRNA expression after the lowering of plasma FFA concentrations in humans, despite an increase in energy expenditure upon beta(2)-adrenergic stimulation.