Lack of β₃-adrenergic effect on lipolysis in human subcutaneous adipose tissue

Human adipocytes are responsive to both α- (antilipolytic) and β-(lipolytic) actions of catecholamine agonists. These effects are mediated by G proteins which interact with adenylylcyclase. β₁- and β₂-adrenoreceptor (AR) subtypes are identified in human adipose tissue. The existence of a third β-adrenergic (β₃) receptor has been recently proposed. The β₃-AR has been reported to mediate catecholamine-induced cAMP accumulation and to be more responsive in this regard than either the β₁- or the β₂-AR. To examine the possibility that a β₃-AR plays a significant role in the control of catecholamine-stimulated lipolysis in human adipose tissue, we used a sensitive in vitro measure of lipolysis. Abdominal and gluteal sc adipose tissue samples from 14 adults were incubated with isoproterenol, a nonspecific β-AR agonist which activates adenylyl cyclase via all three β-AR subtypes, in the presence of varying concentrations of a β-AR antagonist, alprenolol, which blocks the β₁- and β₂-AR, but not the β₃-AR. In tissue from both abdominal and gluteal sites, alprenolol (10^-3 M) completely abolished the lipolytic response to isoproterenol (10^-6 M). Alprenolol (10^-3 M) alone reduced basal lipolysis by 10.2 ± 2.2% (SEM) in abdominal tissue (P < 0.01), and 7.1 ± 2.7% in gluteal tissue (P < 0.05). In the presence of alprenolol (10^-3 M), isoproterenol (10^-6 M) had no demonstrable lipolytic effect. The probability of incorrect acceptance of the null hypothesis that isoproterenol had no effect on lipolysis in alprenolol-blocked tissue is P_β < 0.05 for both depots. As an additional control, pooled inguinal adipose tissue from adult male Sprague-Dawley rats was incubated with the same concentrations of alprenolol. Rat adipose tissue has been previously shown to express the β₃-adrenoreceptor and lipolysis was increased in rat adipose tissue in the presence of alprenolol 10^-4 M and 10^-5 M. We conclude that β₃-ARs, if present in human adipocyte plasma membranes, do not significantly affect rates of lipolysis.