Local insulin-like growth factor-1 and Akt/mTOR signaling in skeletal muscle of lubabegron-supplemented finishing steers.

Lubabegron (LUB) is a β-adrenergic agonist/antagonist approved for reduction of ammonia gas emissions in feedlot cattle; improvements in growth and carcass yield have also been reported, although the underlying mechanism remains unresolved. Thirty-two Angus-influenced steers (524 ± 5 kg) were assigned to control (CON) or LUB diets (3.5 mg/kg dry matter [DM]; targeted 36 mg/steer/d for 63 d). All steers had received a trenbolone acetate-estradiol implant (TE-200) at arrival, 58 d before treatment initiation, administered identically across groups. Growth performance, carcass traits, longissimus muscle (LM) composition, transcriptome, signaling protein abundance, and insulin-like growth factor-1 (IGF-1) were measured. LUB increased final body weight (637 vs. 612 kg), average daily gain, dry matter intake, and gain-to-feed ratio relative to CON (P < 0.01). Hot carcass weight was 18.5 kg greater in LUB (P < 0.01), whereas dressing percentage, REA, 12th-rib fat, and marbling score were unaffected (P ≥ 0.25). LM crude protein was higher (23.6% vs. 22.5%; P < 0.01) and crude fat tended lower (5.0% vs. 6.4%; P = 0.051) in LUB steaks. Warner-Bratzler shear force was greater in LUB at 2 d (4.36 vs. 3.67 kg; P = 0.03) and 14 days (3.74 vs. 2.76 kg; P < 0.01) postmortem. Serum creatinine, total protein, bilirubin, and cholesterol were elevated in LUB steers (P ≤ 0.02). Transcriptomic profiling at d 56 identified 643 differentially expressed genes, with upregulation of myogenic regulators, glycolytic enzymes, and fast-twitch fiber genes and downregulation of adipogenic networks. Phospho-mTOR abundance (P = 0.03) and the p-mTOR/mTOR ratio (P = 0.05) were greater in LUB. Although LUB is an established β3-AR agonist, receptor binding and protein abundance were not assessed; β3-AR transcript in LM was minimal and undetectable in 40.6% of samples, and neither p-CREB nor the phosphorylated-cAMP response element-binding protein CREB (p-CREB)/CREB ratio differed between treatments (P ≥ 0.32), arguing against p-CREB-dependent β3-AR signaling as the primary driver. IGF-1 protein in LM was greater in LUB-supplemented steers at d 56 (P = 0.01), whereas circulating IGF-1 did not differ overall (P = 0.66), although a treatment × time interaction was detected (P < 0.05). The dissociation between elevated local muscle IGF-1 and the absence of a sustained systemic increase supports an autocrine and paracrine IGF-1 mechanism with downstream Akt/mTOR activation as a coherent framework for the muscle response observed with LUB supplementation.