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Lubabegron (LUB; Experior, Elanco, Greenfield, IN, USA) was approved by the U.S. Food and Drug Administration in 2018 and is indicated for the reduction of ammonia (NH3) gas emissions·kg−1 body weight (BW) and hot carcass weight (HCW) when fed to feedlot cattle during the final 14 to 91 d of the finishing period. LUB demonstrates antagonistic behavior at the β 1 and β 2 receptor subtypes and agonistic behavior at the β 3 receptor subtype in cattle and is classified by the Center for Veterinary Medicine as a “beta-adrenergic agonist/antagonist.” This report describes a randomized complete block study that evaluated LUB dose (0, 1.5, 3.5, and 5.5 mg·kg−1 dry matter) during the last 56 d of the feeding period on calculated NH3 gas emissions, live weight, carcass weight, and associated ratios in beef feedlot cattle. Carcass characteristics, mobility, and health were also evaluated. All cattle received monensin and tylosin throughout the study. Ammonia gas emissions were calculated using the equation developed by Brown et al. (Brown, M. S., N. A. Cole, S. Gruber, J. Kube, and J. S. Teeter. 2019. Modeling and prediction accuracy of ammonia gas emissions from feedlot cattle. App. Anim. Sci. 35:347–356). The reduction in calculated cumulative NH3 gas emissions with LUB ranged from 1.3% to 11.0% (85 to 708 g/hd). When NH3 gas emissions were expressed on a live weight (unshrunk) and carcass weight basis, calculated NH3 gas emissions decreased by 3.0% to 12.8% and 3.8% to 14.6%, respectively. Daily dry matter intake was 2.3% greater (Ptrt < 0.05) for steers that received LUB. Average daily gain was 13.7% greater (Ptrt < 0.05; 1.68 vs. 1.91 kg), while gain efficiency was 10.8% greater (Ptrt < 0.05; 0.167 vs. 0.185) for steers fed LUB. Animal mobility was scored in the pen approximately 1 wk prior to harvest, when cattle were loaded on trucks scheduled for harvest, and at antemortem inspection during lairage. No treatment differences (Ptrt ≥ 0.170) were observed at any time for the percent of cattle receiving mobility scores of 1 or 2 (normal or minor stiffness but moving with the normal cattle, respectively). Cattle mobility scored as a 1 or 2 equaled or exceeded 92% at all times. Final BW and HCW increased (Ptrt < 0.05) 11.6 to 15.7 kg and 11.3 to 17.1 kg, respectively, in cattle receiving LUB compared to cattle receiving monensin plus tylosin alone.

Chinese hamster ovary cell constructs expressing either the β 1-, β 2- or β 3-adrenergic receptor (AR) were used to determine whether a novel β-AR modulator, lubabegron fumarate (LUB; Experior, Elanco Animal Health) might exert greater potency for a specific β-AR subtype. EC50 values calculated based on cAMP accumulation in dose response curves indicate that LUB is highly selective for the β 3-AR subtype, with an EC50 of 6 × 10–9 M, with no detectible agonistic activity at the β 2-AR. We hypothesized that the accumulation of lipolytic markers would reflect the agonist activity at each of the β-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 β 1-, β2-, and β 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; β-AR pan-agonist), dobutamine hydrochloride (DOB; specific β 1-AA), salbutamol sulfate (SAL; specific β 2-AA), ractopamine hydrochloride (RAC), zilpaterol hydrochloride (ZIL), BRL-37344 (specific β 3-agonist), or LUB for 30 min following preincubation with theophylline (inhibitor of phosphodiesterase). Relative mRNA amounts for β 1-, β 2-, and β 3-AR were greater (P < 0.05) in s.c. than in i.m. adipose tissue. The most abundant β-AR mRNA in both adipose tissues was the β 2-AR (P < 0.05), with the β 1- and β 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 β-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 β 1- and β 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 β-adrenergic ligands, especially those that are agonists at the β 1- and β3-receptor subtypes. The minimal mRNA expression of the β 1- and β 3 subtypes in i.m. adipose tissue likely limits the response potential to agonists for these β-AR subtypes.

There is a lack of consistency across the globe in how countries establish tissue ractopamine residue limits and which residue limits are applied to various tissues, particularly for edible noncarcass tissues. Therefore, some US beef slaughter organizations have recommended a 48-h voluntary removal of ractopamine before slaughter in order to meet residue requirements of specific export countries and maintain international trade. Our objective was to assess the impact of voluntary removal of ractopamine hydrochloride (Optaflexx®; Elanco, Greenfield, IN) up to 8 d before slaughter on growth performance and carcass characteristics. Crossbred beef steers (60 pens of 10 animals/pen) with an initial shrunk body weight (BW) of 611.8 ± 10 kg SEM were fed one of six treatments over 42 d. Treatments included a control that did not receive ractopamine, on-label use of ractopamine (0-d withdrawal), and 2, 4, 6, or 8 d of voluntary removal of ractopamine from feed before slaughter. The start of ractopamine feeding (30.1 mg/kg of diet dry matter for 32 d) was staggered so that blocks could be slaughtered on the same day. Dry matter intake was decreased by 0.5 kg/d when ractopamine was fed with a 0-d withdrawal (P = 0.04) compared to the control, but was not altered (P = 0.56) as the duration of ractopamine removal increased from 0 to 8 d. Final BW, total BW gain, and average daily BW gain were increased by feeding ractopamine with a 0-d withdrawal (P = 0.09) compared to the control, but these variables decreased in a linear manner (P = 0.10) as the duration of removal increased from 0 to 8 d. Gain efficiency was improved by 15% (P < 0.01) by feeding ractopamine with a 0-d withdrawal compared to the control, and gain efficiency decreased linearly (P = 0.06) as the duration of ractopamine removal increased. Approximately 2/3 of the increase in gain efficiency remained after 8 d of removal. Hot carcass weight was increased by 6 kg (P = 0.02) by feeding ractopamine with a 0-d withdrawal compared to the control. Measured carcass characteristics were not altered by ractopamine feeding or by removal before slaughter (P ≥ 0.24). The consequences of voluntary removal of ractopamine up to 8 d before slaughter were a linear decrease in live BW gain (0.64 kg/d), poorer gain efficiency, and numerically lighter carcass weight.