Metabolomic and Proteomic Profiles Associated With Ketosis in Dairy Cows

Abstract

Ketosis is a common metabolic disease in dairy cows during early lactation. However, information about the metabolomic and proteomic profiles associated with the incidence and progression of ketosis is still limited. In this study, an integrated metabolomics and proteomics approach was performed on blood serum sampled from cows diagnosed with clinical ketosis (case, ≥ 2.60 mmol/L plasma β-hydroxybutyrate; BHBA) and healthy controls (control, < 1.0 mmol/L BHBA). Samples were taken 2 weeks before parturition and 2 weeks after parturition from 19 animals (nine cases, 10 controls). All serum samples (n = 38) were subjected to Liquid Chromatography-Mass Spectrometry (LC-MS) based metabolomic analysis, and 20 samples underwent Data-Independent Acquisition (DIA) LC-MS based proteomic analysis. A total of 97 metabolites and 540 proteins were successfully identified, and multivariate analysis revealed significant differences in both metabolomic and proteomic profiles between cases and controls. We investigated clinical ketosis-associated metabolomic and proteomic changes using statistical analyses. Correlation analysis of statistically significant metabolites and proteins showed 78 strong correlations (correlation coefficient, R ≥ 0.7) between 38 metabolites and 25 proteins, which were then mapped to pathways using IMPaLA. Results showed that ketosis altered a wide range of metabolic pathways, such as metabolism, metabolism of proteins, gene expression and post-translational protein modification, vitamin metabolism, signaling, and disease related pathways. Findings presented here are relevant for identifying molecular targets for ketosis and biomarkers for ketosis detection during the transition period.

Milk proteins as a feed restriction signature indicating the metabolic adaptation of dairy cows

“…Angiotensinogen is the precursor of angiotensin. In dairy cows it has been shown that ketosis may alter the metabolism of angiotensinogen to angiotensin 36 .…”

Integration of Multiplied Omics, a Step Forward in Systematic Dairy Research

“…While Xu et al [ 130 ] found that the plasma concentrations of neurosecretory protein FGA, c1 inhibitor (C1INH), serum amyloid A(SAA), transthyretin (TTR), hepcidin, apoprotein C III (APoCIII), amyloid precursor protein (APP), cystatin C (CysC), osteopontin (OpN) are significantly decreased in cows with fatty liver, not only proved the mitochondria dysfunction of NAFLD. Not only BHBA, the golden standard for ketosis diagnosis, is one of the most altered components in the metabolome profile of ketosis cows [ 48 ], but also serum 4-hydroxy-6-methyl-2-pyrone and cinnamoyl glycine show their potential as ketosis biomarkers [ 131 ]. Ketosis and fatty liver are high susceptive diseases for transition dairy animals and similar to NAFLD, which have been widely researched by omics methods.…”

Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder

“…It was recently reported that 3 metabolic pathways (pyrimidine, ubiquinone, and vitamin K metabolism) were perturbed in children with ASD, with a panel of central nervous system biomarkers (9-hexadecenoylcarnitine [C16:1] and phosphatidylcholine [PC ae-C36:1]) found by metabolomic analysis ( 14 ). Integrated analyses of -omics data have identified potential biomarkers and revealed their interrelationships ( 15 – 18 ). However, to date, there have been no studies that have applied a combination of metabolomic and proteomic approaches to the investigation of ASD etiology.…”