An Bingxing, Liu Peihao, Yang Zhirui, Ying Fan, Liu Dawei, Wen Jie, Zhao Guiping
Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Center for Quantitative Genetics and Genomics (QGG), Aarhus University, Aarhus, 8000, Denmark.
BMC Genomics. 2025 Jul 29;26(1):699. doi: 10.1186/s12864-025-11881-7.
Heat stress (HS) is a significant challenge in poultry, negatively impacting feed efficiency and survival. These adaptive responses could lead to disrupted lipid metabolism, impaired immunity, and neural damage. We hypothesized that the neuroendocrine system plays a central role in HS responses by activating the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes. This study explores the neural transcriptomic changes and metabolomic profile subjected to HS, aiming to unravel the complexity of nervous adaptive responses, including the disrupted lipid metabolism, impaired immunity, and neural damage processes.
Based on the designed chicken HS model, we identified 1,871 serum metabolites, with 149 differentially accumulated metabolites (DAMs), including ursodeoxycholic acid, niacinamide, and prostaglandin E1. These metabolites indicated disrupted lipid homeostasis and potential adaptive mechanisms to mitigate stress. Key metabolite biomarkers were identified using random forest, including 2-(Methylthio)phenol, and Deca-2,4,6-triynedioic acid, enriched in immune and stress-related pathways such as glutathione metabolism and nicotinamide metabolism. Then, the comparative transcriptome analysis of the hypothalamus and pituitary revealed 358 differentially expressed genes (DEGs), highlighting tissue-specific adaptive pattern. The hypothalamus DEGs enriched in neurotransmitter biosynthesis and Notch signaling pathways, while the pituitary DEGs exhibited changes in calcium and insulin signaling pathways. Finally, by integrating omics data with machine learning, we uncovered key stress-relief mechanisms involving adenosine accumulation and adrenaline signaling. Adenosine signaling emerged as a critical pathway for thermoregulation through vascular relaxation, while adrenaline signaling regulated calcium homeostasis and muscle contraction under stress.
This study provides comprehensive insights into the molecular adaptations of HS in broiler, emphasizing the roles of lipid metabolism, neuroendocrine regulation, and vascular dynamics. The findings highlight the potential of integrating transcriptomics and metabolomics with machine learning to identify biomarkers and pathways involved in HS adaptation. These results could provide an effective theoretical basis of the preventive and treatment measures for HS.
热应激（HS）是家禽面临的一项重大挑战，对饲料效率和存活率产生负面影响。这些适应性反应可能导致脂质代谢紊乱、免疫力受损和神经损伤。我们假设神经内分泌系统通过激活下丘脑 - 垂体 - 肾上腺轴和交感 - 肾上腺 - 髓质轴在热应激反应中起核心作用。本研究探讨了热应激下的神经转录组变化和代谢组概况，旨在揭示神经适应性反应的复杂性，包括脂质代谢紊乱、免疫力受损和神经损伤过程。
基于所设计的鸡热应激模型，我们鉴定出1871种血清代谢物，其中有149种差异积累代谢物（DAMs），包括熊去氧胆酸、烟酰胺和前列腺素E1。这些代谢物表明脂质稳态受到破坏以及存在减轻应激的潜在适应机制。使用随机森林鉴定出关键代谢物生物标志物，包括2 - （甲硫基）苯酚和癸 - 2,4,6 - 三炔二酸，它们富集于免疫和应激相关途径，如谷胱甘肽代谢和烟酰胺代谢。然后，下丘脑和垂体的比较转录组分析揭示了358个差异表达基因（DEGs），突出了组织特异性适应模式。下丘脑的DEGs富集于神经递质生物合成和Notch信号通路，而垂体的DEGs在钙和胰岛素信号通路中表现出变化。最后，通过将组学数据与机器学习相结合，我们发现了涉及腺苷积累和肾上腺素信号传导的关键应激缓解机制。腺苷信号传导通过血管舒张成为体温调节的关键途径，而肾上腺素信号传导在应激下调节钙稳态和肌肉收缩。
本研究全面深入地了解了肉鸡热应激的分子适应情况，强调了脂质代谢、神经内分泌调节和血管动力学的作用。研究结果突出了将转录组学和代谢组学与机器学习相结合以识别热应激适应中涉及的生物标志物和途径的潜力。这些结果可为热应激的预防和治疗措施提供有效的理论依据。
