Abstract
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.
Highlights
Most dairy cows experience a period of negative energy balance immediately after calving due to both a reduction in feed intake preceding calving [1], and an increase in energy requirements for milk production [2]
non-esterified fatty acids (NEFA) are transported via the bloodstream to the mammary gland for milk fat synthesis, or to the liver where they undergo either (1) complete oxidation via the TCA cycle, (2) partial oxidation to ketone bodies (BHBA, acetone and acetoacetate), or (3) re-esterification to form triglycerides which can either be stored or exported as very low density lipoprotein (VLDL)
The aim of this study was to use an untargeted 1 H NMR metabolomic approach to investigate the metabolomic fingerprints of serum balance in dairy cows are β-hydroxybutyrate (BHBA) and NEFA concentrations in clinical healthy dairy cows in early lactation, and in so doing (1) identify common and differential metabolic pathways, and (2) identify novel metabotypes for application to genetic selection for improved metabolic health
Summary
Most dairy cows experience a period of negative energy balance immediately after calving due to both a reduction in feed intake preceding calving [1], and an increase in energy requirements for milk production [2]. Metabolites 2020, 10, 247 coordinated changes in metabolism and nutrient partitioning, known as homeorhesis [3] Failure of these homeorhetic controls can lead to the development of metabolic disorders such as ketosis and fatty liver [4]. These disorders can have significant negative effects on the health, welfare and profitability of early-lactation dairy cows due to their (1) relatively high incidence [5,6], (2) demonstrated association with other diseases [4,7] and (3) their significant economic costs [8,9]. Serum β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA) are biomarkers that are commonly used to evaluate the energy balance of dairy cows in the transition period [6,10,11]. BHBA is the most stable of the three ketone bodies [13], and is commonly used as a biomarker of energy balance [14]
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