Characterization Of Beta-Adrenergic Receptors In Bovine Intramuscular And Subcutaneous Adipose Tissue: Comparison Of Lubabegron Fumarate With Beta-Adrenergic Receptor Agonists And Antagonists

Chinese hamster ovary cell constructs expressing either the beta(1)-, beta(2)- or beta(3)-adrenergic receptor (AR) were used to determine whether a novel beta-AR modulator, lubabegron fumarate (LUB; Experior, Elanco Animal Health) might exert greater potency for a specific beta-AR subtype. EC50 values calculated based on cAMP accumulation in dose response curves indicate that LUB is highly selective for the beta(3)-AR subtype, with an EC50 of 6 x 10(-9) M, with no detectible agonistic activity at the beta(2)-AR. We hypothesized that the accumulation of lipolytic markers would reflect the agonist activity at each of the beta-receptor subtypes of the specific ligand; additionally, there would be differences in receptor subtype expression in subcutaneous (s.c.) and intrmuscular (i.m.) adipose tissues. Total RNA was extracted from adipose tissue samples and relative mRNA levels for beta(1)-, beta(2)-, and beta(3)-AR were measured using real-time quantitative polymerase chain reaction. Fresh s.c. and i.m. adipose tissue explants were incubated with isoproterenol hydrochloride (ISO; beta-AR pan-agonist), dobutamine hydrochloride (DOB; specific beta(1)-AA), salbutamol sulfate (SAL; specific beta(2)-AA), ractopamine hydrochloride (RAC), zilpaterol hydrochloride (ZIL), BRL-37344 (specific beta(3)-agonist), or LUB for 30 min following preincubation with theophylline (inhibitor of phosphodiesterase). Relative mRNA amounts for beta(1)-, beta(2)-, and beta(3)-AR were greater (P < 0.05) in s.c. than in i.m. adipose tissue. The most abundant beta-AR mRNA in both adipose tissues was the beta(2)-AR (P < 0.05), with the beta(1)- and beta(3)-AR subtypes being minimally expressed in i.m. adipose tissue. ISO, RH, and ZH stimulated the release of glycerol and nonesterified fatty acid (NEFA) from s.c. adipose tissue, but these beta-AR ligands did not alter concentrations of these lipolytic markers in i.m. adipose tissue. LUB did not affect glycerol or NEFA concentrations in s.c. or i.m. adipose tissue, but attenuated (P < 0.05) the accumulation of cAMP mediated by the beta(1)- and beta(2)-AR ligands DOB and SAL in s.c. adipose tissue. Collectively, these data indicate that bovine i.m. adipose tissue is less responsive than s.c. adipose tissue to beta-adrenergic ligands, especially those that are agonists at the beta(1)- and beta(3)-receptor subtypes. The minimal mRNA expression of the beta(1)- and beta a(3) subtypes in i.m. adipose tissue likely limits the response potential to agonists for these beta-AR subtypes.