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Identification of biomarkers associated with the onset and progression of ketosis in transition dairy cows Open Access


Other title
dairy cows
Type of item
Degree grantor
University of Alberta
Author or creator
Zhang, Guanshi
Supervisor and department
Ametaj, Burim N. (Agricultural, Food, and Nutritional Science)
Examining committee member and department
Zuidhof, Martin (Agricultural, Food, and Nutritional Science)
Yang, Wenzhu (Lethbridge Research and Development Centre; AAFC)
Uwiera, Richard (Agricultural, Food, and Nutritional Science)
Wishart, David S. (Biological Sciences and Computing Science)
Department of Agricultural, Food, and Nutritional Science
Animal Science
Date accepted
Graduation date
2016-06:Fall 2016
Doctor of Philosophy
Degree level
Ketosis is a common metabolic disorder of transition dairy cows during the early lactation period. Cows with ketosis have lower milk yield and reproductive performance, greater risk of other periparturient diseases, and higher culling rate. Although ketosis has been extensively studied, not many investigators have focused on the pathobiology of the disease over time. Previous work has been mainly concentrated on the diagnosis, epidemiology, and implications of ketosis around the transition period. There is a grey area with regards to the agents that initiate ketosis and the metabolic pathways involved in the pathobiology of the disease. Moreover, not very much is known about how to prevent ketosis. Most work has been focused on the treatment of ketotic cows. It would be of great interest to both the dairy industry and health specialists to detect ketosis as early as possible and to take appropriate preventive measures. Therefore, the principal objectives of this thesis are: 1) to find evidence of the involvement of innate immunity in the pathobiology of ketosis as well as changes of in carbohydrate and lipid metabolism in pre-ketotic, ketotic, and post-ketotic cows; 2) to determine blood and urine metabotypes of transition dairy cows before, during, and after occurrence of ketosis; and 3) to identify new screening or predictive metabolite biomarkers of ketosis in the serum and urine of dairy cows as early as 8 weeks before the expected day of parturition. To achieve these objectives, an enzyme linked immunosorbent assay (ELISA) was utilized to quantify and compare selected pro-inflammatory cytokines [i.e., inerleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)], as well as acute phase proteins [(APP), i.e., haptoglobin (Hp) and serum amyloid A (SAA)] in the serum of cows diagnosed postpartum with ketosis and healthy controls (CON) starting at -8 and -4 wks before parturition, during the week of disease diagnosis as well as at +4 wks after calving. We also used several metabolomics tools including direct injection/liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS), proton nuclear magnetic resonance (1H-NMR), gas chromatography-mass spectrometry (GC-MS), and inductively coupled plasma-mass spectrometry (ICP-MS) to quantify and compare metabolites from various analyte groups including amino acids (AAs), acylcarnitines, biogenic amines, glycerophospholipids [i.e., phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC)], sphingolipids [i.e., hydroxysphingomyelin: SM (OH) and sphingomyelin (SM)], hexose, organic acids, saccharides, ketones, alcohols, mineral elements, and others, in the serum/urine of pre-ketotic (-8 and -4 wks), ketotic (disease wk), post-ketotic (+4 and +8 wks), and CON cows. Results of this study indicate that cows affected by ketosis display alterations of multiple variables of innate immunity as well as amino acid, carbohydrate and lipid metabolism several weeks prior to the diagnosis of the disease. Two sets of predictive biomarker models and one diagnostic biomarker model for ketosis with high sensitivity and specificity were identified in serum and urine, respectively. These newly identified sets (two from serum and two from urine) of ketosis biomarkers can predict the disease much earlier than measurement of ketone bodies during early lactation. Results also demonstrated that cows with ketosis experienced lower dry matter intake (DMI), elevated milk somatic cell count (SCC), and a tendency for lower milk production, and lower milk fat.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
Zhang, G., D. Hailemariam, E. Dervishi, S. A. Goldansaz, Q. Deng, S. M. Dunn, and B. N. Ametaj. 2016. Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum. Res. Vet. Sci. 107:246-256.

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