Aarhus University Seal / Aarhus Universitets segl

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. / Wathes, D.C.; Cheng, Z.; Salavati, Mazdak; Buggiotti, L.; Takeda, H.; Tang, L.; Becker, Frank; Ingvartsen, Klaus Lønne; Ferris, Conrad P.; Hostens, Miel; Crowe, Mark A.; GplusE Consortium.

In: Journal of Dairy Science, Vol. 104, No. 3, 03.2021, p. 3596-3616.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Wathes, DC, Cheng, Z, Salavati, M, Buggiotti, L, Takeda, H, Tang, L, Becker, F, Ingvartsen, KL, Ferris, CP, Hostens, M, Crowe, MA & GplusE Consortium 2021, 'Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation', Journal of Dairy Science, vol. 104, no. 3, pp. 3596-3616. https://doi.org/10.3168/jds.2020-19165

APA

Wathes, D. C., Cheng, Z., Salavati, M., Buggiotti, L., Takeda, H., Tang, L., Becker, F., Ingvartsen, K. L., Ferris, C. P., Hostens, M., Crowe, M. A., & GplusE Consortium (2021). Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. Journal of Dairy Science, 104(3), 3596-3616. https://doi.org/10.3168/jds.2020-19165

CBE

Wathes DC, Cheng Z, Salavati M, Buggiotti L, Takeda H, Tang L, Becker F, Ingvartsen KL, Ferris CP, Hostens M, Crowe MA, GplusE Consortium. 2021. Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. Journal of Dairy Science. 104(3):3596-3616. https://doi.org/10.3168/jds.2020-19165

MLA

Vancouver

Wathes DC, Cheng Z, Salavati M, Buggiotti L, Takeda H, Tang L et al. Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. Journal of Dairy Science. 2021 Mar;104(3):3596-3616. https://doi.org/10.3168/jds.2020-19165

Author

Wathes, D.C. ; Cheng, Z. ; Salavati, Mazdak ; Buggiotti, L. ; Takeda, H. ; Tang, L. ; Becker, Frank ; Ingvartsen, Klaus Lønne ; Ferris, Conrad P. ; Hostens, Miel ; Crowe, Mark A. ; GplusE Consortium. / Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation. In: Journal of Dairy Science. 2021 ; Vol. 104, No. 3. pp. 3596-3616.

Bibtex

@article{3d832ed35a424768b71f3c7f38972ad3,
title = "Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation",
abstract = "Homeorhetic 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.",
keywords = "metabolic clustering, RNA sequencing, liver, leukocyte, negative energy balance",
author = "D.C. Wathes and Z. Cheng and Mazdak Salavati and L. Buggiotti and H. Takeda and L. Tang and Frank Becker and Ingvartsen, {Klaus L{\o}nne} and Ferris, {Conrad P.} and Miel Hostens and Crowe, {Mark A.} and {GplusE Consortium} and Leslie Foldager and Torben Larsen and Tine Rousing and Jehan Ettema and S{\o}ren {\O}stergaard and S{\o}rensen, {Martin Tang}",
year = "2021",
month = mar,
doi = "10.3168/jds.2020-19165",
language = "English",
volume = "104",
pages = "3596--3616",
journal = "Journal of Dairy Science",
issn = "0022-0302",
publisher = "Elsevier Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation

AU - Wathes, D.C.

AU - Cheng, Z.

AU - Salavati, Mazdak

AU - Buggiotti, L.

AU - Takeda, H.

AU - Tang, L.

AU - Becker, Frank

AU - Ingvartsen, Klaus Lønne

AU - Ferris, Conrad P.

AU - Hostens, Miel

AU - Crowe, Mark A.

AU - GplusE Consortium

AU - Foldager, Leslie

AU - Larsen, Torben

AU - Rousing, Tine

AU - Ettema, Jehan

AU - Østergaard, Søren

AU - Sørensen, Martin Tang

PY - 2021/3

Y1 - 2021/3

N2 - Homeorhetic 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.

AB - Homeorhetic 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.

KW - metabolic clustering

KW - RNA sequencing

KW - liver

KW - leukocyte

KW - negative energy balance

U2 - 10.3168/jds.2020-19165

DO - 10.3168/jds.2020-19165

M3 - Journal article

C2 - 33455774

VL - 104

SP - 3596

EP - 3616

JO - Journal of Dairy Science

JF - Journal of Dairy Science

SN - 0022-0302

IS - 3

ER -