Thermogenic responsiveness to nonspecific β-adrenergic stimulation is not related to genetic variation in codon 16 of the β2-adrenergic receptor

Abstract

Stimulation of β-adrenergic receptors (β-AR) by the sympathetic nervous system (SNS) modulates energy expenditure (EE), but substantial interindividual variability is observed. We determined whether the thermogenic response to β-AR stimulation is related to genetic variation in codon 16 of the β2-AR, a biologically important β-AR polymorphism, and whether differences in SNS activity (i.e., the stimulus for agonist-promoted downregulation) are involved. The increase in EE (ΔEE, indirect calorimetry, ventilated hood) above resting EE in response to nonspecific β-AR stimulation [iv isoproterenol: 6, 12, and 24 ng/kg fat-free mass (FFM)/min] was measured in 46 healthy adult humans [Arg16Arg: 9 male, 7 female, 48 ± 5 yr; Arg16Gly: 11 male, 4 female, 53 ± 5 yr; Gly16Gly: 3 male, 12 female, 48 ± 5 yr (means ± SE)]. Neither FFM-adjusted baseline resting EE ( P = 0.83) nor the dose of isoproterenol required to increase EE 10% above resting ( P = 0.87) differed among the three groups (Arg16Arg: 5,409 ± 209 kJ/day, 11.2 ± 2.1 ng·kg FFM−1·min−1; Arg16Gly: 5,367 ± 272 kJ/day, 11.1 ± 2.1 ng·kg FFM−1·min−1; Gly16Gly: 5,305 ± 159 kJ/day, 10.5 ± 1.4 ng·kg FFM−1·min−1). Consistent with this, muscle sympathetic nerve activity and plasma norepinephrine concentrations were not different among the groups. Group differences in sex composition did not influence the results. Our findings indicate that the thermogenic response to nonspecific β-AR stimulation, an important mechanistic component of overall β-AR modulation of EE, is not related to this β2-AR polymorphism in healthy humans. This may be explained in part by a lack of association between this gene variant and tonic SNS activity.