Disorders of energy metabolism, which can result from a failure to adapt to the period of negative energy balance immediately after calving, have significant negative effects on the health, welfare and profitability of dairy cows. The most common biomarkers of energy balance in dairy cows are β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA). While elevated concentrations of these biomarkers are associated with similar negative health and production outcomes, the phenotypic and genetic correlations between them are weak. In this study, we used an untargeted ¹H NMR metabolomics approach to investigate the serum metabolomic fingerprints of BHBA and NEFA. Serum samples were collected from 298 cows in early lactation (calibration dataset N = 248, validation N = 50). Metabolomic fingerprinting was done by regressing ¹H NMR spectra against BHBA and NEFA concentrations (determined using colorimetric assays) using orthogonal partial least squares regression. Prediction accuracies were high for BHBA models, and moderately high for NEFA models (R² of external validation of 0.88 and 0.75, respectively). We identified 16 metabolites that were significantly (variable importance of projection score > 1) correlated with the concentration of one or both biomarkers. These metabolites were primarily intermediates of energy, phospholipid, and/or methyl donor metabolism. Of the significant metabolites identified; (1) two (acetate and creatine) were positively correlated with BHBA but negatively correlated with NEFA, (2) nine had similar associations with both BHBA and NEFA, (3) two were correlated with only BHBA concentration, and (4) three were only correlated with NEFA concentration. Overall, our results suggest that BHBA and NEFA are indicative of similar metabolic states in clinically healthy animals, but that several significant metabolic differences exist that help to explain the weak correlations between them. We also identified several metabolites that may be useful intermediate phenotypes in genomic selection for improved metabolic health.

中文翻译：

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两种生物标记物的故事：早期泌乳奶牛中BHBA和NEFA的非靶向1H NMR代谢组学指纹。

产犊后不能立即适应负能量平衡的时期可能导致能量代谢紊乱，这对奶牛的健康，福利和盈利能力产生了显着的负面影响。奶牛中最常见的能量平衡生物标志物是β-羟基丁酸酯（BHBA）和非酯化脂肪酸（NEFA）。虽然这些生物标志物的浓度升高与类似的负面健康和生产结果相关，但它们之间的表型和遗传相关性较弱。在这项研究中，我们使用了非靶向¹ H NMR代谢组学方法来研究BHBA和NEFA的血清代谢组学指纹。在泌乳初期从298头母牛收集血清样本（校准数据集N = 248，验证N= 50）。通过正交偏最小二乘回归BHBA和NEFA浓度（由比色测定确定）的¹ H NMR光谱，进行代谢组学指纹分析。BHBA模型的预测准确性较高，而NEFA模型的预测准确性较高（R ²分别为0.88和0.75的外部验证）。我们鉴定出与一种或两种生物标志物的浓度显着相关（投影得分的可变重要性> 1）的16种代谢物。这些代谢物主要是能量，磷脂和/或甲基供体代谢的中间体。鉴定出的重要代谢产物中；（1）两种（乙酸盐和肌酸）与BHBA正相关，而与NEFA负相关;（2）九种与BHBA和NEFA具有相似的关联;（3）两个仅与BHBA浓度相关;（4）三个仅与NEFA浓度相关。总体而言，我们的结果表明，BHBA和NEFA可以指示临床健康动物体内类似的代谢状态，但是存在一些重要的代谢差异，这有助于解释它们之间的弱相关性。我们还确定了几种可能在基因组选择中用于改善代谢健康的中间表型的代谢物。