Abstract
BackgroundLactation is extremely important for dairy cows; however, the understanding of the underlying metabolic mechanisms is very limited. This study was conducted to investigate the inherent metabolic patterns during lactation using the overall biofluid metabolomics and the metabolic differences from non-lactation periods, as determined using partial tissue-metabolomics. We analyzed the metabolomic profiles of four biofluids (rumen fluid, serum, milk and urine) and their relationships in six mid-lactation Holstein cows and compared their mammary gland (MG) metabolomic profiles with those of six non-lactating cows by using gas chromatography-time of flight/mass spectrometry.ResultsIn total, 33 metabolites were shared among the four biofluids, and 274 metabolites were identified in the MG tissues. The sub-clusters of the hierarchical clustering analysis revealed that the rumen fluid and serum metabolomics profiles were grouped together and highly correlated but were separate from those for milk. Urine had the most different profile compared to the other three biofluids. Creatine was identified as the most different metabolite among the four biofluids (VIP = 1.537). Five metabolic pathways, including gluconeogenesis, pyruvate metabolism, the tricarboxylic acid cycle (TCA cycle), glycerolipid metabolism, and aspartate metabolism, showed the most functional enrichment among the four biofluids (false discovery rate < 0.05, fold enrichment >2). Clear discriminations were observed in the MG metabolomics profiles between the lactating and non-lactating cows, with 54 metabolites having a significantly higher abundance (P < 0.05, VIP > 1) in the lactation group. Lactobionic acid, citric acid, orotic acid and oxamide were extracted by the S-plot as potential biomarkers of the metabolic difference between lactation and non-lactation. The TCA cycle, glyoxylate and dicarboxylate metabolism, glutamate metabolism and glycine metabolism were determined to be pathways that were significantly impacted (P < 0.01, impact value >0.1) in the lactation group. Among them, the TCA cycle was the most up-regulated pathway (P < 0.0001), with 7 of the 10 related metabolites increased in the MG tissues of the lactating cows.ConclusionsThe overall biofluid and MG tissue metabolic mechanisms in the lactating cows were interpreted in this study. Our findings are the first to provide an integrated insight and a better understanding of the metabolic mechanism of lactation, which is beneficial for developing regulated strategies to improve the metabolic status of lactating dairy cows.
Highlights
Lactation is extremely important for dairy cows; the understanding of the underlying metabolic mechanisms is very limited
The inherent metabolic status during lactation and the difference from the nonlactation period are the most important metabolic biological processes for determining milk production and sustainability[2], and they depend on the development of the mammary gland (MG) and the overall coordinated metabolism and physiology
Metabolites identified in biofluids using GC-TOF/MS From the metabolomics datasets of the four biofluids in six lactating cows, 33 shared metabolites were identified in the rumen fluid, serum, milk and urine, including noradrenaline, methylmalonic acid, glycine, lyxose, L-malic acid, thymol, creatine, 5-methoxytryptamine, oxoproline, glycerol, L-threose, m-cresol, aminomalonic acid, 2-hydroxybutanoic acid, alanine, hydroxylamine, phosphate, fumaric acid, glucose, prostaglandin E2, isoleucine, lactose, malonic acid, N-methyl-L-glutamic acid, phenylethylamine, 2,4-diaminobutyric acid, oxalic acid, lactic acid, 4-androsten-1-beta-ol-3,17-dione, norleucine, asparagine, conduritol-b-epoxide, and 5-aminovaleric acid
Summary
Lactation is extremely important for dairy cows; the understanding of the underlying metabolic mechanisms is very limited. This study was conducted to investigate the inherent metabolic patterns during lactation using the overall biofluid metabolomics and the metabolic differences from non-lactation periods, as determined using partial tissue-metabolomics. The inherent metabolic status during lactation and the difference from the nonlactation period are the most important metabolic biological processes for determining milk production and sustainability[2], and they depend on the development of the mammary gland (MG) and the overall coordinated metabolism and physiology. Biofluid metabolomics has been widely used to investigate the relationship between the rumen fluid metabolites and cow health [8], the effect of heat stress on milk metabolites [9], and the urinary biomarkers under different quality forage diets [6]. Identifying the metabolites in the MG during lactation and comparing their key pathways with non-lactating cows could enhance our understanding of the lactation mechanism
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