L-ornithine-L-aspartate enhances protein anabolism and growth performance in broilers by modulating the liver-NH3/Gln-muscle axis

Introduction Dysregulation of hepatic nitrogen metabolism precipitates ammonia (NH 3 ) accumulation, severely compromising broiler growth performance and muscle protein homeostasis via the liver-muscle axis. While L-ornithine-L-aspartate (OA) enhances NH 3 clearance and mitigates sarcopenia in human liver disease, its effects and mechanisms on nitrogen metabolism and muscle development in broilers remain limited. Objectives This study investigated the impact and underlying mechanisms of dietary OA supplementation on white-feathered broilers. Methods Four experiments were conducted using Arbor Acres broilers. Experiments 1 and 2 evaluated dietary OA (0–750 mg/kg) to determine the optimal inclusion rate (400 mg/kg). Experiment 3 established a stable hyperammonemia model via intraperitoneal injection of ammonium acetate. Experiment 4 utilized a 2 × 2 factorial design (0 or 400 mg/kg OA × saline or ammonium acetate challenge) to elucidate OA’s protective mechanisms against NH 3 -induced toxicity. Results OA supplementation (optimally 400 mg/kg) significantly increased body weight and feed conversion efficiency. OA enhanced Gln metabolism by regulating hepatic nitrogen metabolism. Specifically, it promoted Gln synthesis (increased glutamine synthetase activity and Gln levels) and NH 3 detoxification, thereby improving amino acid utilization. Furthermore, OA promoted protein synthesis by activating the hepatic mTOR signaling pathway. At 42 days, 400 mg/kg OA significantly increased breast muscle percentage, improving both growth and slaughter performance. Additionally, OA significantly increased levels of Gln in breast muscle, and effectively reduced NH 3 and myostatin levels, thereby alleviating the suppression of muscle growth. OA also promoted muscle development by increasing protein synthesis and deposition through up-regulating the mTOR signaling pathway and down-regulating NF-κB expression. Conclusion OA safely improves broiler growth and slaughter performance by enhancing Gln production and NH 3 detoxification through the liver-muscle axis, and increasing protein synthesis and deposition. With a confirmed 5-fold safety margin, OA serves as a safe and novel feed additive to optimize nitrogen metabolism in poultry production.