BMC Veterinary Research | |
Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography/mass spectrometry | |
Shi Shu1  Lingwei Sun1  Cheng Xia1  Chuang Xu1  Ling Wu1  Hongyou Zhang1  | |
[1] College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, PR China | |
关键词: Plasma metabolome; Gas chromatography/mass spectrometry; Clinical and subclinical ketosis; Multivariable analysis; | |
Others : 1119452 DOI : 10.1186/1746-6148-9-186 |
|
received in 2013-03-16, accepted in 2013-09-18, 发布年份 2013 | |
【 摘 要 】
Background
Ketosis is an important problem for dairy cows` production performance. However, it is still little known about plasma metabolomics details of dairy ketosis.
Results
A gas chromatography/mass spectrometry (GC/MS) technique was used to investigate plasma metabolic differences in cows that had clinical ketosis (CK, n=22), subclinical ketosis (SK, n=32), or were clinically normal controls (NC, n=22). The endogenous plasma metabolome was measured by chemical derivatization followed by GC/MS, which led to the detection of 267 variables. A two-sample t-test of 30, 32, and 13 metabolites showed statistically significant differences between SK and NC, CK and NC, and CK and SK, respectively. Orthogonal signal correction-partial least-square discriminant analysis (OPLS-DA) revealed that the metabolic patterns of both CK and SK were mostly similar, with the exception of a few differences. The development of CK and SK involved disturbances in many metabolic pathways, mainly including fatty acid metabolism, amino acid metabolism, glycolysis, gluconeogenesis, and the pentose phosphate pathway. A diagnostic model arbitrary two groups was constructed using OPLS-DA and receiver–operator characteristic curves (ROC). Multivariate statistical diagnostics yielded the 19 potential biomarkers for SK and NC, 31 for CK and NC, and 8 for CK and SK with area under the curve (AUC) values. Our results showed the potential biomarkers from CK, SK, and NC, including carbohydrates, fatty acids, amino acids, even sitosterol and vitamin E isomers, etc. 2-piperidinecarboxylic acid and cis-9-hexadecenoic acid were closely associated with metabolic perturbations in ketosis as Glc, BHBA and NEFA for dealing with metabolic disturbances of ketosis in clinical practice. However, further research is needed to explain changes of 2,3,4-trihydroxybutyric acid, 3,4-dihydroxybutyric acid, α-aminobutyric acid, methylmalonic acid, sitosterol and α-tocopherol in CK and SK, and to reveal differences between CK and SK.
Conclusion
Our study shows that some new biomarkers of ketosis from plasma may find new metabolic changes to have clinically new utility and significance in diagnosis, prognosis, and prevention of ketosis in the future.
【 授权许可】
2013 Zhang et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150208070228605.pdf | 1520KB | download | |
Figure 4. | 69KB | Image | download |
Figure 3. | 165KB | Image | download |
Figure 2. | 80KB | Image | download |
Figure 1. | 97KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]Grummer RR: Etiology of lipid-related metabolic disorders in periparturient dairy cows. J Dairy Sci 1993, 76:3882-3896.
- [2]Herdt TH: Ruminant adaptation to negative energy balance. Influences on the etiology of ketosis and fatty liver. Vet Clin North Am Food Anim Pract 2000, 16:215-230.
- [3]Oetzel GR: Monitoring and testing dairy herds for metabolic diseases. Vet Clin North Amer Food Anim Pract 2004, 20:651-674.
- [4]Xia C, Wang Z, Xu C, Zhang HY: Concentrations of plasma metabolites, hormones, and mRNA abundance of adipose leptin and hormone-sensitive lipase in ketotic and nonketotic dairy cows. J Vet Intern Med 2012, 26:415-417.
- [5]Ilves A, Harzia H, Ling K, Ots M, Soomets U, Kilk K: Alterations in milk and blood metabolomes during the first months of lactation in dairy cows. J Dairy Sci 2012, 95:5788-5797.
- [6]Dunn WB, Bailey NJ, Johnson HE: Measuring the metabolome: current analytical technologies. Analyst 2005, 130:606-625.
- [7]Klein MS, Buttchereit N, Miemczyk SP, Immervoll AK, Louis C, Wiedemann S, Junge W, Thaller G, Oefner PJ, Gronwald W: NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis. J Proteome Res 2012, 11:1373-1381.
- [8]Burim NA, Qendrim Z, Fozia S, Psychogios N, Michael JL, Dunn SM, Jianguo X, Wishart DS: Metabolomics reveals unhealthy alterations in rumen metabolism with increased proportion of cereal grain in the diet of dairy cows. Metabolomics 2010, 6(4):583-594.
- [9]Saleem F, Ametaj BN, Bouatra S, Mandal R, Zebeli Q, Dunn SM, Wishart DS: A metabolomics approach to uncover the effects of grain diets on rumen health in dairy cows. J Dairy Sci 2012, 95(11):6606-6623.
- [10]Saleem F, Bouatra S, Chi-Guo A, Psychogios N, Mandal R, Dunn SM, Burim NA, David SW: he bovine ruminal fluid metabolome. Metabolomics 2013, 9(2):360-378.
- [11]Eriksson L, Johansson E, Kettaneh WN, Trygg J, Wikström C, Wold S: Multi- and megavariate data analysis—principles and applications. Umea: UmetricsAB; 2001.
- [12]Nicholson JK, Connelly J, Lindon JC, Holmes E: Metabolomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 2002, 1:153.
- [13]Rajala-Schultz PJ, Gröhn YT, McCulloch CE: Effects of milk fever, ketosis, and lameness on milk yield in dairy cows. J Dairy Sci 1999, 82(2):288-294.
- [14]Gillund P, Reksen O, Gröhn YT, Karlberg K: Body condition related to ketosis and reproductive performance in Norwegian dairy cows. J Dairy Sci 2001, 84(6):1390-1396.
- [15]Lindgren F, Hansen B, Karcher W, Eriksson L: Model validation by permutation tests: Applications to variable selection. J Chemom 1996, 10:521-532.
- [16]Wu H, Xue RY, Dong L, Liu TT, Deng CH, Zeng HZ, Shen XZ: Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry. Anal Chim Acta 2009, 648:98-104.
- [17]Geenen S, Guallar-Hoyas C, Michopoulos F, Kenna JG, Kolaja KL, Westerhoff HV, Thomas P, Wilson ID: HPLC-MS/MS methods for the quantitative analysis of 5-oxoproline (pyroglutamate) in rat plasma and hepatic cell line culture medium. J Pharm Biomed Anal 2011, 56:655-663.
- [18]Bogdanov M, Matson WR, Wang L, Matson T, Pullman RS, Bressman SS, Beal MF: Metabolomic profiling to develop blood biomarkers for Parkinson's disease. Brain 2008, 131:389-396.
- [19]Nelson DL, Cox MM: Lehninger's Principles of Biochemistry. 4th edition. New York: WH. Freeman and Company; 2005.
- [20]Ametaj BN, Emmanuel DG, Zebeli Q, Dunn SM: Feeding high proportions of barley grain in a total mixed ration perturbs diurnal patterns of plasma metabolites in lactating dairy cows. J Dairy Sci 2009, 92:1084-1091.
- [21]King C, Rios G, Green M, Tephly T: UDP-glucuronosyltransferases. Curr Drug Metab 2000, 1:143-161.
- [22]Lankinen M, Schwab U, Seppänen-Laakso T, Mattila I, Juntunen K, Mykkänen H: Poutanen K, Gylling H, Oresic M: Metabolomic analysis of plasma metabolites that may mediate effects of rye bread on satiety and weight maintenance in postmenopausal women. J Nutr 2011, 141:31-36.
- [23]Bosch AM: Classical galactosaemia revisited. J Inherit Metab Dis 2006, 29:516-525.
- [24]Huzzey JM, Nydam DV, Grant RJ, Overton TR: The effects of overstocking Holstein dairy cattle during the dry period on cortisol secretion and energy metabolism. J Dairy Sci 2012, 95:4421-4433.
- [25]Salway JG: Metabolism at a glance. 3rd edition. 350 Main Street, Malden, Massachusetts, 02148-5020, USA: Blackwell Pub Ltd.; 2004.
- [26]Doepel L, Lapierre H, Kenneky JJ: Peripartum performance and metabolism of dairy cows in response to prepartum energy and protein intake. J Dairy Sci 2002, 85:2315-2334.
- [27]Marsh DC, Vreugdenhil PK, Mack VE, Belzer FO, Southard JH: Glycine protects hepatocytes from injury caused by anoxia, cold ischemia and mitochondrial inhibitors, but not injury caused by calcium ionophores or oxidative stress. Hepatology 1993, 17:91-98.
- [28]Marvin DA, Francis B: A Metabolic Study of α-aminobutyric acid. J Biol Chem 1949, 180:1059-1063. Downloaded from http://www.jbc.org/content/180/3/1059.citation webcite
- [29]Hinko CN, Crider AM, Kliem MA, Steinmiller CL, Seo TH, Bin H, Venkatarangan P, EL-assadi AA, Hyejung C, Burns CM, Tietz EI, Andersen PH, Klitgaard H: Anticonvulsant activity of novel derivatives of 2- and 3-piperidinecarboxylic acid in mice and rats. Neuropharm 1996, 35:1721-1735.
- [30]Renée PK, Takhar K, Kathryn AJ, Katherine RT, Adams J, Lisa NB, Gerd K, Brewer WY, Charles RR, Henri B: Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. Am J Physiol Endocrinol Metab 2006, 291:E860-E866.
- [31]Mao YY, Bai JQ, Chen JH, Shou ZF, Qiang H, Wu JY, Chen Y, Cheng YY: A pilot study of GC/MS-based serum metabolic profiling of acute rejection in renal transplantation. Transplant Immunology 2008, 19:74-80.
- [32]Effros RM: Alpha aminobutyric acid, an alternative measure of hepatic injury in sepsis? Transl Res 2011, 158:326-327.
- [33]Ros MM, Sterk SS, Verhagen H, Stalenhoef AF, de Jong N: Phytosterol consumption and the anabolic steroid boldenone in humans: a hypothesis piloted. Food Addit Contam 2007, 24:679-684.
- [34]Wefers HS: The protection of ascorbate and glutathione against microsomal lipid peroxidation is dependent on Vitamin E. Europ J Biochem 1988, 174:353-357.
- [35]Dupriez VJ, Rousseau GG: Glucose response elements in a gene that codes for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. DNA Cell Biol 1997, 16:1075-1085.
- [36]Ferreira G, Weiss WP, Willett LB: Changes in measures of biotin status do not reflect milk yield responses when dairy cows are fed supplemental biotin. J Dairy Sci 2007, 90:1452-1459.
- [37]Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H: GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol 2002, 213:1-47.
- [38]Munro IC, Berndt WO, Borzelleca JF, Flamm G, Lynch BS, Kennepohl E, Bär EA, Modderman J: Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data. Food Chem Toxicol 1998, 36:1139-1174.
- [39]Hamana M, Ohtsuka H, Oikawa M, Kawamura S: Blood free amino acids in the postpartum dairy cattle with left displaced abomasums. J Vet Med Sci 2010, 72:1355-1358.
- [40]Siddiqi NJ, Alhomida AS, Pandey VC: Hydroxyproline distribution in the plasma of various mammals. J Biochem Mol Biol Biophys 2002, 6:159-163.
- [41]Postic C, Dentin R, Girard J: Role of the liver in the control of carbohydrate and lipid homeostasis. Diabetes Metab 2004, 30:398-408.
- [42]Motyl T, Barej W: Plasma amino acid indices and urinary 3-methyl histidine excretion in dairy cows in early lactation. Ann Rech Vet 1986, 17:153-157.
- [43]James W, Croom JR, Bauman DE, Davis CL: Methylmalonic acid in low-fat milk syndrome. J Dairy Sci 1981, 64:649-654.
- [44]Yamashina S, Ikejima K, Enomoto N, Takei Y, Sato N: Glycine as a therapeutic immuno- nutrient for alcoholic liver disease alcohol. Clin Exp Res 2005, 29:162S-165S.
- [45]Joanna KC: Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children. Clinical Biochem 2011, 44:686-691.
- [46]Kim D, Yamagishi N, Ueki A, Miura M, Saito F, Sato S, Furuhama K: Changes in plasma bone metabolic markers in periparturient dairy cows. J Vet Med Sci. 2010, 72:773-776.
- [47]Nishiumi S, Kobayashi T, Ikeda A, Yoshie T, Kibi M, Izumi Y, Okuno T, Hayashi N, Kawano S, Takenawa T, Azuma T, Yoshida M: A novel serum metabolomics-based diagnostic approach for colorectal cancer. PloS ONE 2012, 7(7):e40459.
- [48]Chan EC, Koh PK, Mal M, Cheah PY, Eu KW, Backshall A, Cavill R, Nicholson JK, Keun HC: Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res 2009, 8:352-361.
- [49]Gao XF, Pujos-Guillot E, Sébédio JL: Development of a quantitative metabolomic approach to study clinical human fecal water metabolome based on trimethylsilylation derivatization and GC/MS analysis. Anal Chem 2010, 82:6447-6456.