Exogenous melatonin alleviates heat stress-induced metabolic slowdown affecting broiler growth by improving lipid metabolism.

Heat stress (HS) induces a metabolic slowdown that impairs growth in livestock and poultry. The present study sought to examine the function and underlying mechanisms of melatonin (MT) in mitigating lipid metabolism disorders caused by HS in broiler chickens. Sixty Shengnong 901 broiler chickens were randomly divided into six groups (n = 10), including a control group, a high-dose MT intervention control group (2.0 mg/kg body weight), HS group, and MT low-dose (0.5 mg/kg body weight), medium-dose (1.0 mg/kg body weight), and high-dose (2.0 mg/kg body weight) MT intervention groups. Combining in vivo experiments with network pharmacology analysis, this study elucidates the mechanism by which MT alleviates HS-induced metabolic slowdown affecting broiler growth through regulation of lipid metabolism. The findings indicated that melatonin supplementation markedly enhanced the growth performance of broilers subjected to heat stress. Compared to the HS group, the HSL, HSM, and HSH groups exhibited reduced serum T-CHO, TG, GLU, and LDL levels (P < 0.05), along with decreased hepatic lipid deposition and oxidative damage, indicating MT's capacity to enhance hepatic lipid metabolism under HS conditions. Network pharmacology screening revealed that MT regulates key lipid metabolism targets via the AMPK/PPARα signaling axis. RT-qPCR data demonstrated a significant increase in AMPKα and PPARα expression in the HSM group compared to the HS group (P < 0.01), while key genes in the SREBP1/FASN pathway were downregulated. The study indicates that MT promotes fatty acid oxidation by activating the AMPK/PPARα signaling pathway while simultaneously inhibiting lipid synthesis mediated by SREBP1/FASN, thereby improving hepatic lipid accumulation induced by HS. In conclusion, MT at 1.0 mg/kg body weight is the optimal intervention dose, effectively improving lipid metabolism disorders through multi-target regulation, providing a theoretical basis and practical reference for enhancing poultry resistance to HS.