Skip to main content
Log in

A metabolomics approach to characterize phenotypes of metabolic transition from late pregnancy to early lactation in dairy cows

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Introduction

Dairy cows experience metabolic stress during the transition from late pregnancy to early lactation, due to the complex adaptation processes affecting energy homeostasis in support of milk production, collectively referred to as homeorhesis. According to the individual efficiency of this adaptation, some cows develop severe metabolic diseases while others are able to maintain metabolic health.

Objectives

This study aimed to characterize patterns and changes of metabolic phenotype during the transition period, and to identify how far different metabolic pathways are affected by or contributing to the complex system of homeorhesis.

Methods

Blood samples were collected from 26 German Holstein cows, repeatedly during the transition period: 42 and 10 days before calving and 3, 21 and 100 days after calving. Blood serum samples were subjected to a liquid chromatography–mass spectrometry based targeted metabolomics analysis using the AbsoluteIDQ p180 Kit of Biocrates Life Science AG (Innsbruck, Austria). Processed metabolomics data were evaluated by multivariate data analysis techniques such as principal component analysis (PCA) and partial least squares-discriminant analysis and by heatmap visualization.

Results

The PCA revealed a clear separation according to sampling days, indicating a notable shift of the metabolic phenotype during the transition period. The heatmap showed that acylcarnitines provided a consistent clustering within sampling days, while the concentration of glycerophospholipids and sphingolipids were remarkably decreased 10 days before and 3 days after calving than earlier and later in the transition period.

Conclusion

Analyzing longitudinal changes of the blood metabolome and identifying new biomarkers by this approach can help understanding the multifaceted metabolic adaptation of transition dairy cows.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Adams, S. H., Hoppel, C. L., Lok, K. H., Zhao, L., Wong, S. W., Minkler, P. E., et al. (2009). Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid -oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. Journal of Nutrition, 139(6), 1073–1081. doi:10.3945/jn.108.103754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ametaj, B. N. (2015, May, 8–10). A systems veterinary approach in understanding transition cow diseases: Metabolomics. In: Proceedings of the 4th international symposium on dairy cow nutrition and milk quality, session 1, advances in fundamental research, Beijing (pp. 78–85). May 8–10.

  • Başoğlu, A., Başpinar, N., & Coşkun, A. (2014). NMR-based metabolomic evaluation in dairy cows with displaced abomasum. Turkish Journal of Veterinary and Animal Sciences, 38, 325–330. doi:10.3906/vet-1310-52.

    Article  Google Scholar 

  • Bauman, D. E., & Currie, B. W. (1980). Partitioning of nutrients during pregnancy and lactation: A review of mechanisms involving homeostasis and homeorhesis. Journal of Dairy Science, 63(9), 1514–1529. doi:10.3168/jds.S0022-0302(80)83111-0.

    Article  CAS  PubMed  Google Scholar 

  • Bradford, B. J., Yuan, K., & Ylioja, C. (2016). Managing complexity: Dealing with systemic crosstalk in bovine physiology1. Journal of Dairy Science, 99(6), 4983–4996. doi:10.3168/jds.2015-10271.

    Article  CAS  PubMed  Google Scholar 

  • Butler, W. R. (2000). Nutritional interactions with reproductive performance in dairy cattle. Animal Reproduction Science, 60, 449–457.

    Article  PubMed  Google Scholar 

  • Butler, W. R., & Smith, R. D. (1989). interrelationships between energy balance and postpartum reproductive function in dairy cattle. Journal of Dairy Science, 72(3), 767–783. doi:10.3168/jds.S0022-0302(89)79169-4.

    Article  CAS  PubMed  Google Scholar 

  • De Koster, J. D., & Opsomer, G. (2013). Insulin resistance in dairy cows. Veterinary Clinics of North America: Food Animal Practice, 29(2), 299–322. doi:10.1016/j.cvfa.2013.04.002.

    PubMed  Google Scholar 

  • Drackley, J. K. (1999). Biology of dairy cows during the transition period: The final frontier? Journal of Dairy Science, 82(11), 2259–2273. doi:10.3168/jds.S0022-0302(99)75474-3.

    Article  CAS  PubMed  Google Scholar 

  • Drackley, J. K., Overton, T. R., & Douglas, G. N. (2001). Adaptations of glucose and long-chain fatty acid metabolism in liver of dairy cows during the periparturient period. Journal of Dairy Science, 84, E100–E112. doi:10.3168/jds.S0022-0302(01)70204-4.

    Article  CAS  Google Scholar 

  • Fischer, H. P. (2008). Mathematical modeling of complex biological systems: From parts lists to understanding systems behavior. Alcohol Research & Health, 31(1), 49.

    Google Scholar 

  • Gault, C. R., Obeid, L. M., & Hannun, Y. A. (2010). An overview of sphingolipid metabolism: From synthesis to breakdown. In Sphingolipids as Signaling and Regulatory Molecules (pp. 1–23). New York: Springer. Accessed May 3, 2016 from http://link.springer.com/chapter/10.1007/978-1-4419-6741-1_1

  • Geary, U., Lopez-Villalobos, N., Begley, N., McCoy, F., O’Brien, B., O’Grady, L., et al. (2012). Estimating the effect of mastitis on the profitability of Irish dairy farms. Journal of Dairy Science, 95(7), 3662–3673. doi:10.3168/jds.2011-4863.

    Article  CAS  PubMed  Google Scholar 

  • Goff, J. P., & Horst, R. L. (1997). Physiological changes at parturition and their relationship to metabolic disorders. Journal of Dairy Science, 80(7), 1260–1268. doi:10.3168/jds.S0022-0302(97)76055-7.

    Article  CAS  PubMed  Google Scholar 

  • Ha, C. Y., Kim, J. Y., Paik, J. K., Kim, O. Y., Paik, Y.-H., Lee, E. J., et al. (2012). The association of specific metabolites of lipid metabolism with markers of oxidative stress, inflammation and arterial stiffness in men with newly diagnosed type 2 diabetes: Metabolic intermediates in patients with T2DM. Clinical Endocrinology, 76(5), 674–682. doi:10.1111/j.1365-2265.2011.04244.x.

    Article  CAS  PubMed  Google Scholar 

  • Hailemariam, D., Mandal, R., Saleem, F., Dunn, S. M., Wishart, D. S., & Ametaj, B. N. (2014a). Identification of predictive biomarkers of disease state in transition dairy cows. Journal of Dairy Science, 97(5), 2680–2693. doi:10.3168/jds.2013-6803.

    Article  CAS  PubMed  Google Scholar 

  • Hailemariam, D., Mandal, R., Saleem, F., Dunn, S. M., Wishart, D. S., & Ametaj, B. N. (2014b). Metabolomics approach reveals altered plasma amino acid and sphingolipid profiles associated with patholological state in transition dairy cows. Current Metabolomics, 2(3), 184–195.

    Article  CAS  Google Scholar 

  • Huber, K., Dänicke, S., Rehage, J., Sauerwein, H., Otto, W., Rolle-Kampczyk, U., et al. (2016). Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows. Scientific Reports, 6, 24642. doi:10.1038/srep24642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huber, K., Kenez, A., McNamara, J. P., & Shields, S. L. (2014). A systems approach to determine the effect of changes in gene expression in adipose tissue on productive and reproductive efficiency in dairy cattle. Animal Production Science, 54, 1224–1227. doi:10.1071/AN14209.

    CAS  Google Scholar 

  • Hume, D. A., Whitelaw, C. B. A., & Archibald, A. L. (2011). The future of animal production: Improving productivity and sustainability. The Journal of Agricultural Science, 149(S1), 9–16. doi:10.1017/S0021859610001188.

    Article  Google Scholar 

  • Imhasly, S., Bieli, C., Naegeli, H., Nyström, L., Ruetten, M., & Gerspach, C. (2015). Blood plasma lipidome profile of dairy cows during the transition period. BMC Veterinary Research. doi:10.1186/s12917-015-0565-8.

    PubMed  PubMed Central  Google Scholar 

  • Imhasly, S., Naegeli, H., Baumann, S., von Bergen, M., Luch, A., Jungnickel, H., et al. (2014). Metabolomic biomarkers correlating with hepatic lipidosis in dairy cows. BMC Veterinary Research, 10(1), 1.

    Article  Google Scholar 

  • Inchaisri, C., Jorritsma, R., Vos, P. L. A. M., van der Weijden, G. C., & Hogeveen, H. (2010). Economic consequences of reproductive performance in dairy cattle. Theriogenology, 74(5), 835–846. doi:10.1016/j.theriogenology.2010.04.008.

    Article  CAS  PubMed  Google Scholar 

  • Ingvartsen, K. L. (2006). Feeding- and management-related diseases in the transition cow. Animal Feed Science and Technology, 126(3–4), 175–213. doi:10.1016/j.anifeedsci.2005.08.003.

    Article  Google Scholar 

  • Ingvartsen, K. L., Dewhurst, R. J., & Friggens, N. C. (2003). On the relationship between lactational performance and health: Is it yield or metabolic imbalance that cause production diseases in dairy cattle? A position paper. Livestock Production Science, 83(2), 277–308.

    Article  Google Scholar 

  • Ingvartsen, K. L., & Friggens, N. C. (2005). To what extent do variabilities in hormones, metabolites and energy intake explain variability in milk yield? Domestic Animal Endocrinology, 29(2), 294–304. doi:10.1016/j.domaniend.2005.05.001.

    Article  CAS  PubMed  Google Scholar 

  • Ingvartsen, K. L., & Moyes, K. (2013). Nutrition, immune function and health of dairy cattle. Animal, 7(s1), 112–122. doi:10.1017/S175173111200170X.

    Article  CAS  PubMed  Google Scholar 

  • Kossaibati, M. A., & Esslemont, R. J. (1997). The costs of production diseases in dairy herds in England. The Veterinary Journal, 154(1), 41–51. doi:10.1016/S1090-0233(05)80007-3.

    Article  CAS  PubMed  Google Scholar 

  • LeBlanc, S. (2010). Monitoring metabolic health of dairy cattle in the transition period. Journal of Reproduction and Development, 56(S), S29–S35. doi:10.1262/jrd.1056S29.

    Article  PubMed  Google Scholar 

  • Li, P., Yin, Y.-L., Li, D., Woo Kim, S., & Wu, G. (2007). Amino acids and immune function. British Journal of Nutrition, 98(2), 237. doi:10.1017/S000711450769936X.

    Article  CAS  PubMed  Google Scholar 

  • Loor, J. J., Bertoni, G., Hosseini, A., Roche, J. R., & Trevisi, E. (2013). Functional welfare—using biochemical and molecular technologies to understand better the welfare state of peripartal dairy cattle. Animal Production Science. doi:10.1071/AN12344.

    Google Scholar 

  • Loor, J. J., Vailati-Riboni, M., McCann, J. C., Zhou, Z., & Bionaz, M. (2015). Triennial lactation symposium: Nutrigenomics in livestock: Systems biology meets nutrition. Journal of Animal Science, 93(12), 5554–5574.

    Article  CAS  PubMed  Google Scholar 

  • Maeda, Y., Ohtsuka, H., & Oikawa, M. (2012). Effect of the periparturient period on blood free amino acid concentration in dairy cows/healthy cows. Journal of Veterinary Medicine and Animal Health, 4(9), 124–129.

    CAS  Google Scholar 

  • McCarthy, M. M., Mann, S., Nydam, D. V., Overton, T. R., & McArt, J. A. A. (2015). Short communication: Concentrations of nonesterified fatty acids and β-hydroxybutyrate in dairy cows are not well correlated during the transition period. Journal of Dairy Science, 98(9), 6284–6290. doi:10.3168/jds.2015-9446.

    Article  CAS  PubMed  Google Scholar 

  • McNamara, J. P. (2012). Ruminant nutrition symposium: A systems approach to integrating genetics, nutrition, and metabolic efficiency in dairy cattle. Journal of Animal Science, 90(6), 1846–1854. doi:10.2527/jas.2011-4609.

    Article  CAS  PubMed  Google Scholar 

  • McNamara, J. P. (2015). Triennial lactation symposium: Systems biology of regulatory mechanisms of nutrient metabolism in lactation. Journal of Animal Science, 93(12), 5575–5585.

    Article  CAS  PubMed  Google Scholar 

  • Mulligan, F. J., & Doherty, M. L. (2008). Production diseases of the transition cow. The Veterinary Journal, 176(1), 3–9. doi:10.1016/j.tvjl.2007.12.018.

    Article  CAS  PubMed  Google Scholar 

  • Oltenacu, P. A., & Broom, D. M. (2010). The impact of genetic selection for increased milk yield on the welfare of dairy cows. Animal Welfare, 19(1), 39–49.

    CAS  Google Scholar 

  • Ospina, P. A., McArt, J. A., Overton, T. R., Stokol, T., & Nydam, D. V. (2013). Using nonesterified fatty acids and β-hydroxybutyrate concentrations during the transition period for herd-level monitoring of increased risk of disease and decreased reproductive and milking performance. The Veterinary Clinics of North America. Food Animal Practice, 29(2), 387–412. doi:10.1016/j.cvfa.2013.04.003.

    Article  PubMed  Google Scholar 

  • Reid, I. M., Roberts, C. J., Treacher, R. J., & Williams, L. A. (1986). Effect of body condition at calving on tissue mobilization, development of fatty liver and blood chemistry of dairy cows. Animal Production, 43(1), 7–15. doi:10.1017/S0003356100018298.

    Article  Google Scholar 

  • Rico, J. E., Bandaru, V. V. R., Dorskind, J. M., Haughey, N. J., & McFadden, J. W. (2015). Plasma ceramides are elevated in overweight Holstein dairy cows experiencing greater lipolysis and insulin resistance during the transition from late pregnancy to early lactation. Journal of Dairy Science, 98(11), 7757–7770. doi:10.3168/jds.2015-9519.

    Article  CAS  PubMed  Google Scholar 

  • RStudio Team. (2015). RStudio: Integrated development for R. Boston: RStudio, Inc. http://www.rstudio.com/

  • Sordillo, L. M., & Aitken, S. L. (2009). Impact of oxidative stress on the health and immune function of dairy cattle. Veterinary Immunology and Immunopathology, 128(1–3), 104–109. doi:10.1016/j.vetimm.2008.10.305.

    Article  CAS  PubMed  Google Scholar 

  • Sun, L. W., Zhang, H. Y., Wu, L., Shu, S., Xia, C., Xu, C., et al. (2014). 1H-Nuclear magnetic resonance-based plasma metabolic profiling of dairy cows with clinical and subclinical ketosis. Journal of Dairy Science, 97(3), 1552–1562. doi:10.3168/jds.2013-6757.

    Article  CAS  PubMed  Google Scholar 

  • Tienken, R., Kersten, S., Frahm, J., Meyer, U., Locher, L., Rehage, J., et al. (2015). Effects of an energy-dense diet and nicotinic acid supplementation on production and metabolic variables of primiparous or multiparous cows in periparturient period. Archives of Animal Nutrition, 69(5), 319–339. doi:10.1080/1745039X.2015.1073002.

    Article  CAS  PubMed  Google Scholar 

  • Trevisi, E., Amadori, M., Riva, F., Bertoni, G., & Bani, P. (2014). Evaluation of innate immune responses in bovine forestomachs. Research in Veterinary Science, 96(1), 69–78. doi:10.1016/j.rvsc.2013.11.011.

    Article  CAS  PubMed  Google Scholar 

  • Vernon, R. G. (2005). Lipid metabolism during lactation: A review of adipose tissue–liver interactions and the development of fatty liver. The Journal of Dairy Research, 72(4), 460–469. doi:10.1017/S0022029905001299.

    Article  CAS  PubMed  Google Scholar 

  • Xia, J., Sinelnikov, I. V., Han, B., & Wishart, D. S. (2015). MetaboAnalyst 3.0—Making metabolomics more meaningful. Nucleic Acids Research, 43(W1), W251–W257. doi:10.1093/nar/gkv380.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yea, K., Kim, J., Yoon, J. H., Kwon, T., Kim, J. H., Lee, B. D., et al. (2009). Lysophosphatidylcholine activates adipocyte glucose uptake and lowers blood glucose levels in murine models of diabetes. Journal of Biological Chemistry, 284(49), 33833–33840. doi:10.1074/jbc.M109.024869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, H., Wu, L., Xu, C., Xia, C., Sun, L., & Shu, S. (2013). Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry. BMC Veterinary Research, 9(1), 1.

    Article  CAS  Google Scholar 

  • Zhu, C., Liang, Q., Hu, P., Wang, Y., & Luo, G. (2011). Phospholipidomic identification of potential plasma biomarkers associated with type 2 diabetes mellitus and diabetic nephropathy. Talanta, 85(4), 1711–1720. doi:10.1016/j.talanta.2011.05.036.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ákos Kenéz.

Ethics declarations

Funding

This study was funded by the German Research Foundation (DFG, Bonn, Germany; Grant number DA 558/6-1).

Conflict of interest

Ákos Kenéz, Sven Dänicke, Ulrike Rolle-Kampczyk, Martin von Bergen, Korinna Huber declares that they have no conflict of interest.

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kenéz, Á., Dänicke, S., Rolle-Kampczyk, U. et al. A metabolomics approach to characterize phenotypes of metabolic transition from late pregnancy to early lactation in dairy cows. Metabolomics 12, 165 (2016). https://doi.org/10.1007/s11306-016-1112-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11306-016-1112-8

Keywords

Navigation