Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress

Abstract Background 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...

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Main Authors: Bingxing An, Peihao Liu, Zhirui Yang, Fan Ying, Dawei Liu, Jie Wen, Guiping Zhao
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Genomics
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Online Access:https://doi.org/10.1186/s12864-025-11881-7
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author Bingxing An
Peihao Liu
Zhirui Yang
Fan Ying
Dawei Liu
Jie Wen
Guiping Zhao
author_facet Bingxing An
Peihao Liu
Zhirui Yang
Fan Ying
Dawei Liu
Jie Wen
Guiping Zhao
author_sort Bingxing An
collection DOAJ
description Abstract Background 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. Results 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. Conclusions 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.
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spelling doaj-art-cbc02e6af16248b5befd54c9028ec81c2025-08-20T03:42:37ZengBMCBMC Genomics1471-21642025-07-0126111510.1186/s12864-025-11881-7Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stressBingxing An0Peihao Liu1Zhirui Yang2Fan Ying3Dawei Liu4Jie Wen5Guiping Zhao6Institute of Animal Sciences of Chinese Academy of Agricultural SciencesInstitute of Animal Sciences of Chinese Academy of Agricultural SciencesInstitute of Animal Sciences of Chinese Academy of Agricultural SciencesMiLe Xinguang Agricultural and Animal Industrials CorporationMiLe Xinguang Agricultural and Animal Industrials CorporationInstitute of Animal Sciences of Chinese Academy of Agricultural SciencesInstitute of Animal Sciences of Chinese Academy of Agricultural SciencesAbstract Background 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12864-025-11881-7BiomarkersHeat stressMetabolomics and transcriptomicsNeuroendocrine regulation
spellingShingle Bingxing An
Peihao Liu
Zhirui Yang
Fan Ying
Dawei Liu
Jie Wen
Guiping Zhao
Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress
BMC Genomics
Biomarkers
Heat stress
Metabolomics and transcriptomics
Neuroendocrine regulation
title Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress
title_full Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress
title_fullStr Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress
title_full_unstemmed Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress
title_short Integrative transcriptomics and metabolomics reveal neuroendocrine-lipid crosstalk and adenosine signaling in broiler under heat stress
title_sort integrative transcriptomics and metabolomics reveal neuroendocrine lipid crosstalk and adenosine signaling in broiler under heat stress
topic Biomarkers
Heat stress
Metabolomics and transcriptomics
Neuroendocrine regulation
url https://doi.org/10.1186/s12864-025-11881-7
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