Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation.

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dc.contributor.authorWathes, D.C.
dc.contributor.authorCheng, Z.
dc.contributor.authorSalavati, M.
dc.contributor.authorBuggiotti, L.
dc.contributor.authorTakeda, H.
dc.contributor.authorTang, L.
dc.contributor.authorBecker, F.
dc.contributor.authorIngvartsen, K.I.
dc.contributor.authorFerris, Conrad P.
dc.contributor.authorHostens, M.
dc.contributor.authorCrowe, M.A.
dc.contributor.authorGplusE Consortium
dc.date.accessioned2021-03-26T12:33:23Z
dc.date.available2021-03-26T12:33:23Z
dc.date.issued2021-01-15
dc.descriptionPublication history: Accepted - 11 October 2020; Published online - 15 January 2021en_US
dc.description.abstractHomeorhetic mechanisms assist dairy cows in the transition from pregnancy to lactation. Less successful cows develop severe negative energy balance (NEB), placing them at risk of metabolic and infectious diseases and reduced fertility. We have previously placed multiparous Holstein Friesian cows from 4 herds into metabolic clusters, using as biomarkers measurements of plasma nonesterified fatty acids, β-hydroxybutyrate, glucose and IGF-1 collected at 14 and 35 d in milk (DIM). This study characterized the global transcriptomic profiles of liver and circulating leukocytes from the same animals to determine underlying mechanisms associated with their metabolic and immune function. Liver biopsy and whole-blood samples were collected around 14 DIM for RNA sequencing. All cows with available RNA sequencing data were placed into balanced (BAL, n = 44), intermediate (n = 44), or imbalanced (IMBAL, n = 19) metabolic cluster groups. Differential gene expression was compared between the 3 groups using ANOVA, but only the comparison between BAL and IMBAL cows is reported. Pathway analysis was undertaken using DAVID Bioinformatic Resources (https://david.ncifcrf.gov/). Milk yields did not differ between BAL and IMBAL cows but dry matter intake was less in IMBAL cows and they were in greater energy deficit at 14 DIM (−4.48 v −11.70 MJ/d for BAL and IMBAL cows). Significantly differentially expressed pathways in hepatic tissue included AMPK signaling, glucagon signaling, adipocytokine signaling, and insulin resistance. Genes involved in lipid metabolism and cholesterol transport were more highly expressed in IMBAL cows but IGF1 and IGFALS were downregulated. Leukocytes from BAL cows had greater expression of histones and genes involved in nucleosomes and cell division. Leukocyte expression of heat shock proteins increased in IMBAL cows, suggesting an unfolded protein response, and several key genes involved in immune responses to pathogens were upregulated (e.g., DEFB13, HP, OAS1Z, PTX3, and TLR4). Differentially expressed genes upregulated in IMBAL cows in both tissues included CD36, CPT1, KFL11, and PDK4, all central regulators of energy metabolism. The IMBAL cows therefore had greater difficulty maintaining glucose homeostasis and had dysregulated hepatic lipid metabolism. Their energy deficit was associated with a reduced capacity for cell division and greater evidence of stress responses in the leukocyte population, likely contributing to an increased risk of infectious disease.en_US
dc.description.sponsorshipThis project received funding from the European Union's Seventh Framework Programme (Brussels, Belgium) for research, technological development, and demonstration under grant agreement no. 613689en_US
dc.identifierhttp://hdl.handle.net/20.500.12518/225
dc.identifier.citationWathes, D. C., Cheng, Z., Salavati, M., Buggiotti, L., Takeda, H., Tang, L., Becker, F., Ingvartsen, K. I., Ferris, C., Hostens, M. and Crowe, M. A. (2021) ‘Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation’, Journal of Dairy Science. American Dairy Science Association, 104(3), pp. 3596–3616. doi: 10.3168/jds.2020-19165.en_US
dc.identifier.issn1525-3198
dc.identifier.urihttps://doi.org/10.3168/jds.2020-19165
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rights© 2021, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.subjectmetabolic clusteringen_US
dc.subjectRNA sequencingen_US
dc.subjectliveren_US
dc.subjectleukocyteen_US
dc.subjectnegative energy balanceen_US
dc.titleRelationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation.en_US
dc.typeArticleen_US
dcterms.dateAccepted2020-10-11
dcterms.dateSubmitted2020-06-26

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