Haptoglobin, Magnesium, Adiponectin, and Leptin as Biomarkers for Obesity and Insulin Dysregulation in Horses
Relation of Biomarkers with Obesity and Insulin in Horses
Keywords:
horse, obesity, adiponectin, leptin, haptoglobin, insulin dysregulationAbstract
The aim of this project was to identify blood analytes which are associated with obesity and/or insulin dysregulation (ID) in horses. For this study, 57 horses were selected. At the start, body condition score (BCS) was established, and an oral sugar test (OST) was performed. Furthermore, the following blood analytes were determined: basal glucose, insulin, albumin, high molecular weight (HMW) adiponectin, leptin, haptoglobin, total protein, calcium, magnesium, phosphate, non-esterified fatty acids, and also glucose and insulin 75 min after an OST. Horses were classified according to their body condition as ‘lean’ (BCS 4/9-6/9) or ‘obese’ (BCS > 6/9). Horses were classified as insulin dysregulated (ID-positive) when insulin was 40 mU/L or higher than 75 min after OST. Multivariable logistic regression analysis showed a correlation between obesity and HMW adiponectin, leptin, total protein, and magnesium and between ID, haptoglobin, and leptin. Receiver operating characteristic plots (ROC) of obesity with leptin, adiponectin, total protein, and magnesium, which had an area under the curve (AUC) of 0.932, showed that the combination of these four blood analytes has a high association with obesity. The AUC of the ROC analysis of ID with haptoglobin and leptin was 0.805 implicating that this combination has a high association with ID. Although obesity can be observed (eyes and hands), the health risk of obesity can be monitored with a combination of leptin, adiponectin, total protein, and magnesium, while leptin and haptoglobin are good markers for ID (a health risk of obesity).
References
Gunnink C. [The Netherlands Horse Country: Equestrian Sports and Key Figures] 2016.
Graaf-Roelfsema ED. [Is Being Overweight a Disease?] 2012.
Radin MJ, Sharkey LC, Holycross BJ. Adipokines: A Review of Biological and Analytical Principles and an Update in Dogs, Cats, and Horses. Veterinary Clinical Pathology 2009;38:136–56. https://doi.org/10.1111/j.1939-165X.2009.00133.x.
Suagee JK, Corl BA, Crisman MV, Pleasant RS, Thatcher CD, Geor RJ. Relationships Between Body Condition Score and Plasma Inflammatory Cytokines, Insulin, and Lipids in a Mixed Population of Light-Breed Horses. Journal of Veterinary Internal Medicine 2013;27:157–63. https://doi.org/10.1111/jvim.12021.
Dugdale AHA, Grove-White D, Curtis GC, Harris PA, Argo CM. Body Condition Scoring as a Predictor of Body Fat in Horses and Ponies. Vet J 2012;194:173–8. https://doi.org/10.1016/j.tvjl.2012.03.024.
Bertin FR, de Laat MA. The Diagnosis of Equine Insulin Dysregulation. Equine Veterinary Journal 2017;49:570–6. https://doi.org/10.1111/evj.12703.
Frank N, Tadros EM. Insulin Dysregulation. Equine Veterinary Journal 2014;46:103–12. https://doi.org/10.1111/evj.12169.
EMS Working Group. Recommendations for the Diagnosis and Treatment of Equine Metabolic Syndrome (EMS) 2016.
Gordon ME, McKeever KH, Betros CL, Manso Filho HC. Exercise-Induced Alterations in Plasma Concentrations of Ghrelin, Adiponectin, Leptin, Glucose, Insulin, and Cortisol in Horses. The Veterinary Journal 2007;173:532–40. https://doi.org/10.1016/j.tvjl.2006.01.003.
Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity. Biochem Biophys Res Commun 1999;257:79–83. https://doi.org/10.1006/bbrc.1999.0255.
Bamford NJ, Potter SJ, Harris PA, Bailey SR. Effect of Increased Adiposity on Insulin Sensitivity and Adipokine Concentrations in Horses and Ponies Fed a High Fat Diet, With or Without a Once Daily High Glycaemic Meal. Equine Vet J 2016;48:368–73. https://doi.org/10.1111/evj.12434.
Bastard JP, Vidal H, Jardel C, Bruckert E, Robin D, Vallier P, et al. Subcutaneous Adipose Tissue Expression of Plasminogen Activator Inhibitor-1 Gene During Very Low Calorie Diet in Obese Subjects. Int J Obes Relat Metab Disord 2000;24:70–4. https://doi.org/10.1038/sj.ijo.0801087.
Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, et al. Regulation of Adiponectin by Adipose Tissue-Derived Cytokines: In Vivo and In Vitro Investigations in Humans. American Journal of Physiology-Endocrinology and Metabolism 2003;285:E527–33. https://doi.org/10.1152/ajpendo.00110.2003.
Kearns CF, McKeever KH, Roegner V, Brady SM, Malinowski K. Adiponectin and Leptin Are Related to Fat Mass in Horses. The Veterinary Journal 2006;172:460–5. https://doi.org/10.1016/j.tvjl.2005.05.002.
Kearns CF, Mckeever KH, Kumagai K, Abe T. Fat-Free Mass Is Related to One-Mile Race Performance in Elite Standardbred Horses. The Veterinary Journal 2002;163:260–6. https://doi.org/10.1053/tvjl.2001.0656.
Chameroy K. Diagnosis and Management of Horses with Equine Metabolic Syndrome (EMS). Doctoral Dissertations 2010.
Fain JN, Bahouth SW, Madan AK. Haptoglobin Release by Human Adipose Tissue in Primary Culture. Journal of Lipid Research 2004;45:536–42. https://doi.org/10.1194/jlr. M300406-JLR200.
Maffei M, Barone I, Scabia G, Santini F. The Multifaceted Haptoglobin in the Context of Adipose Tissue and Metabolism. Endocrine Reviews 2016;37:403–16. https://doi.org/10.1210/er.2016-1009.
Geor RJ. Metabolic Predispositions to Laminitis in Horses and Ponies: Obesity, Insulin Resistance and Metabolic Syndromes. Journal of Equine Veterinary Science 2008;28:753–9. https://doi.org/10.1016/j.jevs.2008.10.016.
Johnson PJ, Wiedmeyer CE, LaCarrubba A, Ganjam VKS, Messer NT. Diabetes, Insulin Resistance, and Metabolic Syndrome in Horses. J Diabetes Sci Technol 2012;6:534–40. https://doi.org/10.1177/193229681200600307.
Selim S, Elo K, Jaakkola S, Karikoski N, Boston R, Reilas T, et al. Relationships Among Body Condition, Insulin Resistance and Subcutaneous Adipose Tissue Gene Expression During the Grazing Season in Mares. PLOS ONE 2015;10:e0125968. https://doi.org/10.1371/journal.pone.0125968.
Ungru J, Coenen M, Vervuert I, Blüher M, Raila J, Boston R. Effects of Body Weight Reduction on Blood Adipokines and Subcutaneous Adipose Tissue Adipokine mRNA Expression Profiles in Obese Ponies. Veterinary Record 2012;171:528–528. https://doi.org/10.1136/vr.100911.
Van Den Wollenberg L, Vandendriessche V, van Maanen K, Counotte GHM. Comparison of Two Diagnostic Methods To Detect Insulin Dysregulation in Horses Under Field Conditions. Journal of Equine Veterinary Science 2020;88:102954. https://doi.org/10.1016/j.jevs.2020.102954.
Carroll CL, Huntington PJ. Body Condition Scoring and Weight Estimation of Horses. Equine Vet J 1988;20:41–5. https://doi.org/10.1111/j.2042-3306.1988.tb01451.x.
Carter RA, Geor RJ, Burton Staniar W, Cubitt TA, Harris PA. Apparent Adiposity Assessed by Standardised Scoring Systems and Morphometric Measurements in Horses and Ponies. Vet J 2009;179:204–10. https://doi.org/10.1016/j.tvjl.2008.02.029.
Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, et al. ECEIM Consensus Statement on Equine Metabolic Syndrome. Journal of Veterinary Internal Medicine 2019;33:335–49. https://doi.org/10.1111/jvim.15423.
CBS. More Diabetics in Obese Population. Statistics Netherlands 2016. https://www.cbs.nl/en-gb/news/2016/45/more-diabetics-in-obese-population (accessed January 18, 2022).
Gatineau M, Hancock C, Holman N, Outhwaite H. Adult Obesity and Type 2 Diabetes 2014.
Burns TA, Geor RJ, Mudge MC, McCutcheon LJ, Hinchcliff KW, Belknap JK. Proinflammatory Cytokine and Chemokine Gene Expression Profiles in Subcutaneous and Visceral Adipose Tissue Depots of Insulin-Resistant and Insulin-Sensitive Light Breed Horses. Journal of Veterinary Internal Medicine 2010;24:932–9. https://doi.org/10.1111/j.1939-1676.2010.0551.x.
Nadler JL, Buchanan T, Natarajan R, Antonipillai I, Bergman R, Rude R. Magnesium Deficiency Produces Insulin Resistance and Increased Thromboxane Synthesis. Hypertension 1993;21:1024–9. https://doi.org/10.1161/01.hyp.21.6.1024.
Stewart AJ. Magnesium Disorders in Horses. Veterinary Clinics of North America: Equine Practice 2011;27:149–63. https://doi.org/10.1016/j.cveq.2010.12.009.
Díez JJ, Iglesias P. The Role of the Novel Adipocyte-Derived Hormone Adiponectin in Human Disease. Eur J Endocrinol 2003;148:293–300. https://doi.org/10.1530/eje.0.1480293.
Pratt SE, Geor RJ, McCutcheon LJ. Relationship of Insulin Sensitivity to Aerobic Capacity in Standardbred Mares and Geldings. Equine and Comparative Exercise Physiology 2005;2:185–93. https://doi.org/10.1079/ECP200550.
Menzies-Gow NJ, Harris PA, Elliott J. Prospective Cohort Study Evaluating Risk Factors for the Development of Pasture-Associated Laminitis in the United Kingdom. Equine Veterinary Journal 2017;49:300–6. https://doi.org/10.1111/evj.12606.
Buff PR, Dodds AC, Morrison CD, Whitley NC, McFadin EL, Daniel JA, et al. Leptin in Horses: Tissue Localization and Relationship Between Peripheral Concentrations of Leptin and Body Condition. Journal of Animal Science 2002;80:2942–8. https://doi.org/10.2527/2002.80112942x.
Karikoski NP, Box JR, Mykkänen AK, Kotiranta VV, Raekallio MR. Variation in Insulin Response to Oral Sugar Test in a Cohort of Horses Throughout the Year and Evaluation of Risk Factors for Insulin Dysregulation. Equine Vet J 2021. https://doi.org/10.1111/evj.13529.
Menzies-Gow NJ, Knowles EJ, Rogers I, Rendle DI. Validity and Application of Immunoturbidimetric and Enzyme-Linked Immunosorbent Assays for the Measurement of Adiponectin Concentration in Ponies. Equine Vet J 2019;51:33–7. https://doi.org/10.1111/evj.12960.
Chutia H, Lynrah KG. Association of Serum Magnesium Deficiency with Insulin Resistance in Type 2 Diabetes Mellitus. J Lab Physicians 2015;7:075–8. https://doi.org/10.4103/0974-2727.163131.
Fried SK, Bunkin DA, Greenberg AS. Omental and Subcutaneous Adipose Tissues of Obese Subjects Release Interleukin-6: Depot Difference and Regulation by Glucocorticoid1. The Journal of Clinical Endocrinology & Metabolism 1998;83:847–50. https://doi.org/10.1210/jcem.83.3.4660.
Kędzierski W. Changes in Plasma Leptin Concentration During Different Types of Exercises Performed by Horses. Animal 2014;8:1456–61. https://doi.org/10.1017/S1751731114001220.
Pleasant R s., Suagee J k., Thatcher C d., Elvinger F, Geor R j. Adiposity, Plasma Insulin, Leptin, Lipids, and Oxidative Stress in Mature Light Breed Horses. Journal of Veterinary Internal Medicine 2013;27:576–82. https://doi.org/10.1111/jvim.12056.
De Pergola G, Di Roma P, Paoli G, Guida P, Pannacciulli N, Giorgino R. Haptoglobin Serum Levels Are Independently Associated With Insulinemia in Overweight and Obese Women. J Endocrinol Invest 2007;30:399–403. https://doi.org/10.1007/BF03346317.
Kosolofski HR, Gow SP, Robinson KA. Prevalence of Obesity in the Equine Population of Saskatoon and Surrounding Area. Can Vet J 2017;58:967–70.
Wooldridge AA, Edwards HG, Plaisance EP, Applegate R, Taylor DR, Taintor J, et al. Evaluation of High–Molecular Weight Adiponectin in Horses. American Journal of Veterinary Research 2012;73:1230–40. https://doi.org/10.2460/ajvr.73.8.1230.
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Dr. Guillaume Counotte, Prof. Andy Durham, Dr. Veerle Vandendriessche, Dr. Linda van den Wollenberg
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain the copyright of their manuscripts, and all Open Access articles are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.
