---

Metabolic syndrome in horses is a multifactorial pathological condition characterized by abdominal obesity, insulin resistance, hormonal dysfunctions, and chronic low-grade inflammation. A key aspect in the pathogenesis of this syndrome is the imbalance of adipokines, particularly leptin and adiponectin, which may play a crucial role in the development of metabolic disturbances. The aim of this study was to determine the changes in leptin, adiponectin levels, and their ratio (leptin-to-adiponectin ratio, LAR) in horses with varying degrees of body condition and to evaluate their association with insulin resistance development.

The study involved 18 clinically healthy horses aged 5–10 years, divided into a control group (n=9; body condition score [BCS] 4–6 according to Henneke scale) and an obese group (n=9; BCS ≥7). Serum concentrations of adiponectin and leptin were measured by enzyme-linked immunosorbent assay (ELISA), along with glucose and insulin levels. Insulin sensitivity index (RISQI) and LAR were calculated.

Results demonstrated that obese horses had significantly higher leptin levels (p<0.001) and significantly lower adiponectin concentrations compared to controls. This resulted in more than a threefold increase in LAR (p<0.001), indicating marked disruption of hormonal regulation of adipose tissue. Additionally, elevated glycemia, hyperinsulinemia, and decreased RISQI values were observed, confirming insulin resistance in overweight horses.

These findings suggest that LAR can serve as a sensitive early biomarker of metabolic distress and insulin resistance in horses. Its use is recommended for early identification of at-risk animals, monitoring the effectiveness of preventive measures, and substantiating personalized strategies for diet and physical activity modification aimed at preventing complications associated with metabolic syndrome.

 

References

Beyazıt, F., & Ünsal, M. A. (2017). Obesity and insulin resistance are significant predictors of serum leptin levels. Journal of the Turkish German Gynecological Association, 18(3), 158–159. https://doi.org/10.4274/jtgga.2017.0027.

Buff, P. R., Dodds, A. C., Morrison, C. D., Whitley, N. C., McFadin, E. L., Daniel, J. A., Djiane, J., & Keisler, D. H. (2002). Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition. Journal of animal science, 80(11), 2942–2948. https://doi.org/10.2527/2002.80112942x.

Cornier, M. A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008). The metabolic syndrome. Endocrine reviews, 29(7), 777–822. https://doi.org/10.1210/er.2008-0024.

Correia, M. L., & Rahmouni, K. (2006). Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes, obesity & metabolism, 8(6), 603–610. https://doi.org/10.1111/j.1463-1326.2005.00562.x.

de Git, K. C. G., Peterse, C., Beerens, S., Luijendijk, M. C. M., van der Plasse, G., la Fleur, S. E., & Adan, R. A. H. (2018). Is leptin resistance the cause or the consequence of diet-induced obesity?. International journal of obesity (2005), 42(8), 1445–1457. https://doi.org/10.1038/s41366-018-0111-4.

Després, J. P., & Lemieux, I. (2006). Abdominal obesity and metabolic syndrome. Nature, 444(7121), 881–887. https://doi.org/10.1038/nature05488.

Eckel, R. H., Grundy, S. M., & Zimmet, P. Z. (2005). The metabolic syndrome. Lancet (London, England), 365(9468), 1415–1428. https://doi.org/10.1016/S0140-6736(05)66378-7.

Esteghamati, A., Khalilzadeh, O., Anvari, M., Rashidi, A., Mokhtari, M., & Nakhjavani, M. (2009). Association of serum leptin levels with homeostasis model assessment-estimated insulin resistance and metabolic syndrome: the key role of central obesity. Metabolic syndrome and related disorders, 7(5), 447–452. https://doi.org/10.1089/met.2008.0100.

Frühbeck, G., Catalán, V., Rodríguez, A., & Gómez-Ambrosi, J. (2018). Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte, 7(1), 57–62. https://doi.org/10.1080/21623945.2017.1402151.

Frühbeck, G., Catalán, V., Rodríguez, A., Ramírez, B., Becerril, S., Salvador, J., Portincasa, P., Colina, I., & Gómez-Ambrosi, J. (2017). Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome. Scientific reports, 7(1), 6619. https://doi.org/10.1038/s41598-017-06997-0.

Gairolla, J., Kler, R., Modi, M., & Khurana, D. (2017). Leptin and adiponectin: pathophysiological role and possible therapeutic target of inflammation in ischemic stroke. Reviews in the neurosciences, 28(3), 295–306. https://doi.org/10.1515/revneuro-2016-0055.

Galic, S., Oakhill, J. S., & Steinberg, G. R. (2010). Adipose tissue as an endocrine organ. Molecular and cellular endocrinology, 316(2), 129–139. https://doi.org/10.1016/j.mce.2009.08.018.

Gauff, F., Patan-Zugaj, B., & Licka, T. F. (2013). Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit. Equine veterinary journal, 45(5), 613–618. https://doi.org/10.1111/evj.12040.

Gutch, M., Kumar, S., Razi, S., Gupta, K., & Gupta, A. (2015). Assessment of insulin sensitivity/resistance. Indian journal of endocrinology and metabolism, 19(1), 160. http://dx.doi.org/10.4103/2230-8210.146874.

Han, S. K., Seo, M. J., Lee, T., & Kim, M. Y. (2024). Effectiveness of the ALT/AST ratio for predicting insulin resistance in a Korean population: A large-scale, cross-sectional cohort study. PloS one, 19(5), e0303333. https://doi.org/10.1371/journal.pone.0303333.

Harker, I. J., Harris, P. A., & Barfoot, C. F. (2011). The body condition score of leisure horses competing at an unaffiliated championship in the UK. Journal of Equine Veterinary Science, 31(5‒6), 253–254. http://dx.doi.org/10.1016/j.jevs.2011.03.058.

Hart, K. A., Wochele, D. M., Norton, N. A., McFarlane, D., Wooldridge, A. A., & Frank, N. (2016). Effect of age, season, body condition, and endocrine status on serum free cortisol fraction and insulin concentration in horses. Journal of veterinary internal medicine, 30(2), 653–663. https://doi.org/10.1111/jvim.13839.

Hemat Jouy, S., Mohan, S., Scichilone, G., Mostafa, A., & Mahmoud, A. M. (2024). Adipokines in the crosstalk between adipose tissues and other organs: implications in cardiometabolic diseases. Biomedicines, 12(9), 2129. https://doi.org/10.3390/biomedicines12092129.

Kamei, N., Tobe, K., Suzuki, R., Ohsugi, M., Watanabe, T., Kubota, N., Ohtsuka-Kowatari, N., Kumagai, K., Sakamoto, K., Kobayashi, M., Yamauchi, T., Ueki, K., Oishi, Y., Nishimura, S., Manabe, I., Hashimoto, H., Ohnishi, Y., Ogata, H., Tokuyama, K., Tsunoda, M., … Kadowaki, T. (2006). Overexpression of monocyte chemoattractant protein‑1 in adipose tissues causes macrophage recruitment and insulin resistance. The Journal of biological chemistry, 281(36), 26602–26614. https://doi.org/10.1074/jbc.M601284200.

Kang, Y., Park, H. J., Kang, M. I., Lee, H. S., Lee, S. W., Lee, S. K., & Park, Y. B. (2013). Adipokines, inflammation, insulin resistance, and carotid atherosclerosis in patients with rheumatoid arthritis. Arthritis research & therapy, 15(6), R194. https://doi.org/10.1186/ar4384.

Kaufman, K. L., Suagee-Bedore, J. K., Johnson, S. E., Ely, K. M., Ghajar, S. J., & McIntosh, B. M. (2025). Horses with previous episodes of laminitis have altered insulin responses to seasonal oral sugar testing and grazing compared to horses with no known history of laminitis. Journal of equine veterinary science, 145, 105254. https://doi.org/10.1016/j.jevs.2024.105254.

Khan, M., & Joseph, F. (2014). Adipose tissue and adipokines: the association with and application of adipokines in obesity. Scientifica, 2014, 328592. https://doi.org/10.1155/2014/328592.

Krause, M. P., Liu, Y., Vu, V., Chan, L., Xu, A., Riddell, M. C., Sweeney, G., & Hawke, T. J. (2008). Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function. American journal of physiology. Cell physiology, 295(1), C203–C212. https://doi.org/10.1152/ajpcell.00030.2008.

Liu, Y., Palanivel, R., Rai, E., Park, M., Gabor, T. V., Scheid, M. P., Xu, A., & Sweeney, G. (2015). Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin sensitivity during high-fat diet feeding in mice. Diabetes, 64(1), 36–48. https://doi.org/10.2337/db14-0267.

Mark, A. L., Correia, M. L., Rahmouni, K., & Haynes, W. G. (2002). Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications. Journal of hypertension, 20(7), 1245–1250. https://doi.org/10.1097/00004872-200207000-00001.

Marycz, K., Kornicka, K., Szlapka-Kosarzewska, J., & Weiss, C. (2018). Excessive endoplasmic reticulum stress correlates with impaired mitochondrial dynamics, mitophagy and apoptosis, in liver and adipose tissue, but not in muscles in EMS horses. International journal of molecular sciences, 19(1), 165. http://dx.doi.org/10.3390/ijms19010165.

Monteiro, R., & Azevedo, I. (2010). Chronic inflammation in obesity and the metabolic syndrome. Mediators of inflammation, 2010, 289645. https://doi.org/10.1155/2010/289645.

Moonishaa, T., Nanda, S., Shamraj, M., Sivaa, R., Sivakumar, P., & Ravichandran, K. (2017). Evaluation of leptin as a marker of insulin resistance in type 2 diabetes mellitus. International journal of applied and basic medical research, 7(3), 176. http://dx.doi.org/10.4103/ijabmr.ijabmr_278_16.

Napoli, G., Pergola, V., Basile, P., De Feo, D., Bertrandino, F., Baggiano, A., Mushtaq, S., Fusini, L., Fazzari, F., Carrabba, N., Rabbat, M. G., Motta, R., Ciccone, M. M., Pontone, G., & Guaricci, A. I. (2023). Epicardial and pericoronary adipose tissue, coronary inflammation, and acute coronary syndromes. Journal of clinical medicine, 12(23), 7212. https://doi.org/10.3390/jcm12237212.

Nguyen T. M. D. (2020). Adiponectin: Role in Physiology and Pathophysiology. International journal of preventive medicine, 11, 136. https://doi.org/10.4103/ijpvm.IJPVM_193_20.

Oda, N., Imamura, S., Fujita, T., Uchida, Y., Inagaki, K., Kakizawa, H., Hayakawa, N., Suzuki, A., Takeda, J., Horikawa, Y., & Itoh, M. (2008). The ratio of leptin to adiponectin can be used as an index of insulin resistance. Metabolism: clinical and experimental, 57(2), 268–273. https://doi.org/10.1016/j.metabol.2007.09.011.

Qiao, L., Kinney, B., Yoo H. S., Lee, B., Schaack, J., & Shao, J. (2012). Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1. Diabetes, 61(6), 1463–1470. https://doi.org/10.2337/db11-1475.

Radin, M. J., Sharkey, L. C., & Holycross, B. J. (2009). Adipokines: a review of biological and analytical principles and an update in dogs, cats, and horses. Veterinary clinical pathology, 38(2), 136–156. https://doi.org/10.1111/j.1939-165X.2009.00133.x.

Rasouli, N., & Kern, P. A. (2008). Adipocytokines and the metabolic complications of obesity. The Journal of clinical endocrinology and metabolism, 93(11 Suppl 1), S64–S73. https://doi.org/10.1210/jc.2008-1613.

Reilly, M. P., Iqbal, N., Schutta, M., Wolfe, M. L., Scally, M., Localio, A. R., Rader, D. J., & Kimmel, S. E. (2004). Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. The Journal of clinical endocrinology and metabolism, 89(8), 3872–3878. https://doi.org/10.1210/jc.2003-031676.

Robin, C. A., Ireland, J. L., Wylie, C. E., Collins, S. N., Verheyen, K. L., & Newton, J. R. (2015). Prevalence of and risk factors for equine obesity in Great Britain based on owner-reported body condition scores. Equine veterinary journal, 47(2), 196–201. https://doi.org/10.1111/evj.12275.

Rueda-Clausen, C. F., Lahera, V., Calderón, J., Bolivar, I. C., Castillo, V. R., Gutiérrez, M., Carreño, M., Oubiña, M.delP., Cachofeiro, V., & López-Jaramillo, P. (2010). The presence of abdominal obesity is associated with changes in vascular function independently of other cardiovascular risk factors. International journal of cardiology, 139(1), 32–41. https://doi.org/10.1016/j.ijcard.2008.09.005.

Tian, F., Luo, R., Zhao, Z., Wu, Y., & Ban, D.j (2010). Blockade of the RAS increases plasma adiponectin in subjects with metabolic syndrome and enhances differentiation and adiponectin expression of human preadipocytes. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 118(4), 258–265. https://doi.org/10.1055/s-0029-1237706.

Tong, H. V., Luu, N. K., Son, H. A., Hoan, N. V., Hung, T. T., Velavan, T. P., & Toan, N. L. (2017). Adiponectin and pro-inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus. Journal of diabetes investigation, 8(3), 295–305. https://doi.org/10.1111/jdi.12579.

Wang, B., Guo, H., Li, X., Yue, L., Liu, H., Zhao, L., Bai, H., Liu, X., Wu, X., & Qu, Y. (2018). Adiponectin attenuates oxygen-glucose deprivation-induced mitochondrial oxidative injury and apoptosis in hippocampal HT22 cells via the JAK2/STAT3 Pathway. Cell transplantation, 27(12), 1731–1743. https://doi.org/10.1177/0963689718779364.

Wang, Y., Ali, Y., Lim, C. Y., Hong, W., Pang, Z. P., & Han, W. (2014). Insulin-stimulated leptin secretion requires calcium and PI3K/Akt activation. The Biochemical journal, 458(3), 491–498. https://doi.org/10.1042/BJ20131176.

Wannamethee, S. G., Tchernova, J., Whincup, P., Lowe, G. D., Kelly, A., Rumley, A., Wallace, A. M., & Sattar, N. (2007). Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease. Atherosclerosis, 191(2), 418–426. https://doi.org/10.1016/j.atherosclerosis.2006.04.012.

Wasim, M., Awan, F. R., Najam, S. S., Khan, A. R., & Khan, H. N. (2016). Role of leptin deficiency, inefficiency, and leptin receptors in obesity. Biochemical genetics, 54(5), 565–572. https://doi.org/10.1007/s10528-016-9751-z.

Wray, H., Elliott, J., Bailey, S. R., Harris, P. A., & Menzies-Gow, N. J. (2013). Plasma concentrations of inflammatory markers in previously laminitic ponies. Equine veterinary journal, 45(5), 546–551. https://doi.org/10.1111/evj.12031.

Wyse, C. A., McNie, K. A., Tannahill, V. J., Murray, J. K., & Love, S. (2008). Prevalence of obesity in riding horses in Scotland. The Veterinary record, 162(18), 590–591. https://doi.org/10.1136/vr.162.18.590.

Yadav, A., Kataria, M. A., Saini, V., & Yadav, A. (2013). Role of leptin and adiponectin in insulin resistance. Clinica chimica acta; international journal of clinical chemistry, 417, 80–84. https://doi.org/10.1016/j.cca.2012.12.007.

Zhang, L., Yuan, M., Zhang, L., Wu, B., & Sun, X. (2019). Adiponectin alleviates NLRP3-inflammasome-mediated pyroptosis of aortic endothelial cells by inhibiting FoxO4 in arteriosclerosis. Biochemical and biophysical research communications, 514(1), 266–272. https://doi.org/10.1016/j.bbrc.2019.04.143.

Zhao, S., Kusminski, C. M., Elmquist, J. K., & Scherer, P. E. (2020). Leptin: Less Is More. Diabetes, 69(5), 823–829. https://doi.org/10.2337/dbi19-0018.

Zhou, Y., & Rui, L. (2013). Leptin signaling and leptin resistance. Frontiers of medicine, 7(2), 207–222. https://doi.org/10.1007/s11684-013-0263-5.

Мельник, А. А., Фурман, О. В., Руденко, А. А., Дзісь, Н. П., Хитрук, К. М., & Хитрук, С. В. (2024). Порівняння інформативності індексів HOMA та Матсуда, як провідних діагностичних показників інсулінорезистентності. Клінічна та профілактична медицина, (7), 38‒43. https://doi.org/10.31612/2616-4868.7.2024.04.