Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

FGF-21: promising biomarker for detecting ketosis in dairy cows

Abstract

The objective of this study was to investigate the measurement of serum fibroblast growth factor-21 (FGF-21), a protein mainly synthesized by the liver, as a sensitive biomarker for diagnosis of ketosis in dairy cows. Ninety Holstein–Friesian dairy cows (60 healthy and 30 ketosis cases) were selected and divided into a Ketosis group (K), and a Control group (C). We measured serum FGF-21 and other biochemical parameters by commercial ELISA kits. In a combined population of all 90 cows, we found that serum FGF-21 level was lower (P < 0.001) in cows suffering from ketosis. When the β-hydroxybutyric acid (BHBA) level increased over 1.2 mmol/L, the FGF-21 level tended to decline below 300.85 pg/ml. The area under the receiver operating characteristic curve (AUC-ROC) for serum FGF-21 for diagnosis of fatty liver was 0.952–0.025 [95 % confidence interval (CI) 0.904, 1.000] which was higher than the AUC-ROC for glucose (Glc) and other tested parameters. We concluded that FGF-21 could be a diagnostic parameter in the evaluation and auxiliary diagnosis of changes in the energy metabolism state, and serum FGF-21 measurement would have a considerable clinical impact and lead to greater profitability in the dairy industry.

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

Fig. 1

References

  1. Badman MK, Pissios P et al (2007) Hepatic fibroblast growth factor 21 is regulated by 27 PPAR alpha and is a Key mediator of hepatic lipid metabolism in Ketotic States. Cell Metab 5:426–437

  2. Bobbert T, Schwarz F, Fischer-Rosinsky A (2013) Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians. Diabetes Care 36:145–149

  3. Burke CM, Leslie KE, Neuder LM (2008) Test comparison of precision Xtra and Ketostix for ketosis in dairy cows. Proc Am Assoc Bov Pract 41:287

  4. Carrier J, Stewart S, Godden S, Fetrow J et al (2004) Evaluation and use of three cow-side tests for detection of subclinical ketosis in early postpartum cows. J Dairy Sci 87:3725–3735

  5. Chau MD, Yang Q, Gromada J (2010) Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci U S A 107(28):12553–8

  6. De Roos AP, Van den Bijgaart HJ, Horlyk J et al (2007) Screening for subclinical ketosis in dairy cattle by fourier transform infrared spectrometry. J Dairy Sci 90:1761–1766

  7. Divers TJ, Peek SF (2008) Rebhun’s diseases of dairy cattle, 2nd edn. Saunders Elsevier, St. Louis

  8. Duffield TF (2000) Subclinical ketosis in lactating dairy cattle: metabolic disorders of ruminants. Vet Clin North Am Food Anim Pract 16:231–53

  9. Duffield TF, Lissemore KD, Mcbride BW et al (2009) Impact of hyperketonemia in early lactation dairy cows on health and production. J Dairy Sci 92(2):571–580

  10. Fisher FM, Chui PC, Antonellis PJ (2010) Obesity is a fibroblast growth factor 21 (FGF-21)-resistant state. Diabetes 59:2781–2789

  11. Gilman C, Lundhsen T et al (2008) The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARaipha activation in man. Cell Metab 8(2):169–74

  12. Herdt TH (2000) Variability characteristics and test selection in herd-level nutritional and metabolic profile testing: metabolic disorders of ruminants. Vet Clin North Am Food Anim Pract 16:387–403

  13. Hondares E, Iglesias R, Giralt A (2011) Thermogenic activation induces FGF-21 expression and release in brown adipose tissue. J Biol Chem 286:12983–90

  14. Iwersen M, Falkenberg U, Voigtsberger R et al (2009) Evaluation of an electronic Cowside test to detect subclinical ketosis in dairy cows. J Dairy Sci 92:2618–24

  15. Kharitonenkov A, Shiyanova TL, Koester A (2012) FGF-21 as a novel metabolic regulator. J Clin Invest 115:1627–35

  16. Kliewer SA, Mangelsdorf DJ (2010) Fibroblast growth factor 21: from pharmacology to physiology. Am J Clin Nutr 91(1):254S–257S

  17. Kralisch S, Fasshauer M (2011) Fibroblast growth factor 21: effects on carbohydrate and lipid metabolism in health and disease. Curr Opin Clin Nutr Metab Care 14(4):354–9

  18. Lenart-Lipinska M, Matyjaszek-Matuszek B, Gernand W (2013) Serum fibroblast growth factor 21 is predictive of combined cardiovascular morbidity and mortality in patients with type 2 diabetes at a relatively short-term follow-up. Diabetes Res Clin Pract 101:194–200

  19. Li H, Dong K, Fang Q (2013) High serum level of fibroblast growth factor 21 is an independent predictor of non-alcoholic fatty liver disease: a 3-year prospective study in China. J Hepatol 58:557–563

  20. Liu H, Wu T (2003) Estimating the area under a receiver operating characteristic curve (ROC) for repeated measures design. J Stat Softw 8:1–18

  21. Maxin G, Glasser F, Hurtaud C, Peyraud JL (2011) Combined effects of trans-10, cis-12 conjugated linoleic acid, propionate, andacetate on milk fat yield and composition in dairy cows. J Dairy Sci 94:2051–2059

  22. McArt JA, Nydam DV, Ospina PA et al (2011) A field trial on the effect of propylene glycol on milk yield and resolution of ketosis in fresh cows diagnosed with subclinical ketosis. J Dairy Sci 94:6011–20

  23. Mraz M, Bartlova M, Lacinova Z (2009) Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin Endocrinol 71(3):369–375

  24. Nishimura T, Nakatake Y, Konishi M (2000) Identification of a novel FGF, FGF-21, preferentially expressed in the liver. Biochim Biophys Acta 1492:203–206

  25. Oetzel GR (2004) Monitoring and testing dairy herds for metabolic disease. Vet Clin North Am Food Anim Pract 20:651–74

  26. Oetzel GR, McGuirk SM (2008) Evaluation of a hand-held meter for Cow-side evaluation of blood Betahydroxybutyrate and glucose concentrations in dairy cows. Proc Am Assoc Bov Pract 41:234

  27. Osorio JS, Trevisi E, Ballou MA (2013) Effect of the level of maternal energy intake prepartum on immunometabolic markers, polymorphonuclear leukocyte function, and neutrophil gene network expression in neonatal Holstein heifer calves. J Dairy Sci 96:3573–3587

  28. Ospina PA, Nydam DV, Stokol T et al (2010) Evaluation of Nonesterified fatty acids and Betahydroxybutyrate in transition dairy cattle in the northeastern united states: critical thresholds for prediction of clinical diseases. J Dairy Sci 93:546–54

  29. Potthoff MJ, Inagaki T, Satapati S (2009) FGF-21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proc Natl Acad Sci U S A 106(26):10853–8

  30. Schoenberg KM, Giesy SL, Harvatine KJ (2011) Plasma FGF-21 is elevated by the intense lipid mobilization of lactation. Endocrinology 152:4652–61

  31. Tomohiro Y, Kazutaka M, Jun You L et al (2005) Modulation of growth hormone pulsatility by sex steroids in female goats. Endocrinology 146(6):2736–2743

  32. Uebanso T, Taketani Y, Yamamoto H (2011) Paradoxical regulation of human FGF-21 by both fasting and feeding signals: is FGF-21a nutritional adaptation factor? PLoS One 6(8):22976

  33. Van Knegsel AT, van Derft SG, Horneman M et al (2010) Short communication: ketone body concentration in milk determined by Fourier transform infrared spectroscopy: value for the detection of hyperketonemia in dairy cows. J Dairy Sci 93(7):3065–3069

  34. Vilà-Brau A, De Sousa-Coelho AL, Mayordomo C (2011) Human HMGCS2 regulates mitochondrial fatty acid oxidation and FGF-21 expression in HepG2 cell line. J Biol Chem 286:20423–20430

  35. Xu J, Lloyd DJ, Hale C (2009) Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58(1):250–259

  36. Yang M, Dong J, Liu H et al (2011) Effects of short-term continuous subcutaneous insulin infusion on fasting plasma fibroblast growth factor-21 levels in patients with newly diagnosed type 2 diabetes mellitus. Plos One 6(10):e26359

  37. Zhang ZG, Liu GW, Li XB et al. (2009) β-Hydroxybutyrate, glucose, calcium, phosphorus, and vitamin C concentrations in blood of dairy cows with subclinical ketosis during the early lactation.. Bulletin of the Veterinary Institute in Pulawy, (1):71–74

Download references

Acknowledgments

This research was supported by National Nature Science Foundation of China (31372625), National Key Technology Support Program (2013BAD21B01), The Fok Ying-Tong Education Foundation, China (141021), and New Century Excellent Talents in University (1252-NCET-003). I would like to thank Thomas A. Gavin, Professor Emeritus, Cornell University, for help with editing the English in this paper.

Author information

Correspondence to Chuang Xu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Chuang Xu and Qiushi Xu contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xu, C., Xu, Q., Chen, Y. et al. FGF-21: promising biomarker for detecting ketosis in dairy cows. Vet Res Commun 40, 49–54 (2016). https://doi.org/10.1007/s11259-015-9650-5

Download citation

Keywords

  • Serum FGF-21
  • Ketosis
  • Blood metabolites
  • Diagnosis