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多组学揭示了奶牛酮病早期的血液差异代谢物和差异基因。

Multiomics reveals blood differential metabolites and differential genes in the early onset of ketosis in dairy cows.

机构信息

College of Animal Science and Technology, Ningxia Hui Autonomous Region Key Laboratory of Ruminant Molecular Cell and Breeding, Ningxia University, Yinchuan 750021, China.

College of Animal Science and Technology, Ningxia Hui Autonomous Region Key Laboratory of Ruminant Molecular Cell and Breeding, Ningxia University, Yinchuan 750021, China.

出版信息

Genomics. 2024 Sep;116(5):110927. doi: 10.1016/j.ygeno.2024.110927. Epub 2024 Aug 24.

DOI:10.1016/j.ygeno.2024.110927
PMID:39187030
Abstract

Ketosis-a metabolic state characterized by elevated levels of ketone bodies in the blood or urine-reduces the performance and health of dairy cows and causes substantial economic losses for the dairy industry. Currently, beta-hydroxybutyric acid is the gold standard for determining ketosis in cows; however, as this method is only applicable postpartum, it is not conducive to the early intervention of ketosis in dairy cows. In this study, the sera of dry, periparturient, postpartum ketotic, and healthy cows were analyzed by both transcriptomics and metabolomics techniques. Moreover, changes of gene expression and metabolites were observed, and serum physiological and biochemical indexes were detected by ELISA. The purpose was to screen biomarkers that can be used to detect the incidence of dry or periparturient ketosis in cows. The results showed that ketotic cows had increased levels of glycolipid metabolism indexes, oxidizing factors, and inflammatory factors during dry periods and liver damage, which could be used as early biomarkers to predict the onset of ketosis. Transcriptomic results yielded 20 differentially expressed genes (DEGs) between ketotic and healthy cows during dry, peripartum, and postpartum periods. GO and KEGG enrichment analyses indicated that these DEGs were involved in amino acid metabolism, energy metabolism, and disease-related signaling pathways. The metabolomics sequencing results showed that ketotic cows mainly showed enrichment in tricarboxylic acid cycle, butyric acid metabolism, carbon metabolism, lysine degradation, fatty acid degradation, and other signaling pathways. Metabolites differed between ketotic and healthy cows in dry, pre-parturition, and post-parturition periods. Combined transcriptomics and metabolomics analyses identified significant enrichment in the glucagon signaling pathway and the lysine degradation signaling pathway in dry, periparturient, and postpartum ketotic cows. PRKAB2 and SETMAR-key DEGs of the glucagon signaling pathway and lysine degradation signaling pathway, respectively-can be used as key marker genes for determining the early onset of ketosis in dairy cows.

摘要

酮症——一种以血液或尿液中酮体水平升高为特征的代谢状态——会降低奶牛的生产性能和健康水平,并给奶牛养殖业造成巨大的经济损失。目前,β-羟丁酸是确定奶牛酮症的金标准;然而,由于这种方法仅适用于产后,不利于奶牛酮症的早期干预。在这项研究中,我们使用转录组学和代谢组学技术分析了干奶牛、围产期奶牛、产后酮病奶牛和健康奶牛的血清。此外,还观察了基因表达和代谢物的变化,并通过 ELISA 检测了血清生理生化指标。目的是筛选可用于检测奶牛干奶期或围产期酮病发生的生物标志物。结果表明,酮病奶牛在干奶期和围产期的糖脂代谢指标、氧化因子和炎症因子升高,可作为预测酮病发生的早期标志物。转录组学结果显示,在干奶期、围产期和产后,酮病奶牛与健康奶牛之间有 20 个差异表达基因(DEGs)。GO 和 KEGG 富集分析表明,这些 DEGs 参与了氨基酸代谢、能量代谢和疾病相关的信号通路。代谢组学测序结果表明,酮病奶牛主要在三羧酸循环、丁酸代谢、碳代谢、赖氨酸降解、脂肪酸降解等信号通路中富集。在干奶期、围产期和产后,酮病奶牛与健康奶牛的代谢物存在差异。转录组学和代谢组学联合分析发现,在干奶期、围产期和产后酮病奶牛中,胰高血糖素信号通路和赖氨酸降解信号通路显著富集。PRKAB2 和 SETMAR——分别是胰高血糖素信号通路和赖氨酸降解信号通路的关键 DEG——可以作为确定奶牛酮病早期发生的关键标记基因。

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