Adipose tissue dysfunction in obese horses with equine metabolic syndrome.
Abstract: Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. Objective: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. Methods: Cross-sectional post-mortem study. Methods: Samples of peri-renal (visceral) and retroperitoneal adipose tissue were obtained at post-mortem from healthy horses (n = 9) and horses with EMS (n = 6). Samples were analysed to determine average adipocyte size, fibrotic content and expression of inflammatory and insulin signalling genes. Results: Horses with metabolic syndrome showed marked adipocyte hypertrophy and increased expression of adipokines (leptin) and inflammatory cytokines (TNFα, IL1β and CCL2) in both adipose tissue depots compared to healthy horses. There were no differences in fibrosis or expression of genes relating to insulin signalling between the groups. Conclusions: Cases used in this study had advanced EMS and may represent the end stage of the condition; the design of the study is such that we were unable to relate the identified adipose tissue dysfunction to whole body insulin dysregulation. Conclusions: Horses with obesity and EMS have significant dysfunction of the peri-renal and retroperitoneal adipose tissue that may contribute to whole body insulin dysregulation.
© 2019 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Publication Date: 2019-04-10 PubMed ID: 30866087PubMed Central: PMC6850304DOI: 10.1111/evj.13097Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The aim of this study was to investigate whether obese horses with equine metabolic syndrome (EMS) have dysfunctional adipose tissue, indicated by enlarged fat cells, inflammation, and altered insulin signalling. The study found that EMS horses do indeed have adipocyte hypertrophy, increased expression of adipokines, and inflammatory cytokines in their adipose tissue, suggesting adipose tissue dysfunction that could play a role in overall insulin regulation.
Research Objectives and Methods
- The research was designed to test the hypothesis that obese horses with EMS have adipose tissue dysfunction. This was characterised by several disorders including adipocyte hypertrophy (overgrown fat cells), fibrosis (excess fibrous connective tissue), inflammation, and irregular insulin signalling.
- Researchers conducted a cross-sectional study post-mortem, taking samples of two types of adipose tissue – peri-renal (visceral) and retroperitoneal – from both healthy horses (9 in number) and those diagnosed with EMS (6 in number).
- In the lab, scientists measured the average adipocyte size, fibrotic content, and expression of inflammatory and insulin signalling genes in the tissue samples.
Key Findings
- The obese horses with EMS demonstrated significant adipocyte hypertrophy, indicating an excessive growth of fat cells that can be connected with metabolic syndrome. In addition, the expressions of adipokines (proteins produced by fat cells) and inflammatory cytokines (TNFα, IL1β, and CCL2) were amplified in the adipose tissue samples when compared to healthy horses.
- Surprisingly, the study found no differences in fibrosis or expression of genes relating to insulin signalling between healthy horses and those with EMS. This suggests that while obesity and EMS may cause some adipose tissue dysfunction in horses, it does not affect all aspects of adipose tissue health or function.
Study Limitations and Conclusions
- The study’s design did not allow researchers to definitively link the identified adipose tissue dysfunction to whole body insulin dysregulation.
- It’s important to note that the cases used in this study were advanced EMS horses, which could mean the observed adipose tissue dysfunction might represent the end stage of the condition.
- However, the study concludes that there is a significant dysfunction of the peri-renal and retroperitoneal adipose tissue in horses with obesity and EMS. This adipose tissue dysfunction could be a contributing factor to whole body insulin dysregulation in EMS horses.
Cite This Article
APA
Reynolds A, Keen JA, Fordham T, Morgan RA.
(2019).
Adipose tissue dysfunction in obese horses with equine metabolic syndrome.
Equine Vet J, 51(6), 760-766.
https://doi.org/10.1111/evj.13097 Publication
Researcher Affiliations
- Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, UK.
- Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, UK.
- Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, UK.
- Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, UK.
- University/BHF Centre for Cardiovascular Science, the Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
MeSH Terms
- Adipose Tissue / metabolism
- Animals
- Case-Control Studies
- Cross-Sectional Studies
- Horse Diseases / physiopathology
- Horses
- Metabolic Syndrome / physiopathology
- Metabolic Syndrome / veterinary
- Obesity / veterinary
Grant Funding
- R42126/82976 / BBSRC/Pfizer CASE Studentship
- 206587/Z/17/Z / Wellcome Trust
- British Heart Foundation Centre of Excellence Award
References
This article includes 41 references
- Frank N, Geor RJ, Bailey SR, Durham AE, Johnson PJ. Equine metabolic syndrome.. J Vet Intern Med 2010 May-Jun;24(3):467-75.
- Owers R, Chubbock S. Fight the fat!. Equine Vet J 2013 Jan;45(1):5.
- Tandon P, Wafer R, Minchin JEN. Adipose morphology and metabolic disease.. J Exp Biol 2018 Mar 7;221(Pt Suppl 1).
- Arner E, Westermark PO, Spalding KL, Britton T, Rydén M, Frisén J, Bernard S, Arner P. Adipocyte turnover: relevance to human adipose tissue morphology.. Diabetes 2010 Jan;59(1):105-9.
- Kabir M, Stefanovski D, Hsu IR, Iyer M, Woolcott OO, Zheng D, Catalano KJ, Chiu JD, Kim SP, Harrison LN, Ionut V, Lottati M, Bergman RN, Richey JM. Large size cells in the visceral adipose depot predict insulin resistance in the canine model.. Obesity (Silver Spring) 2011 Nov;19(11):2121-9.
- Hoffstedt J, Arner E, Wahrenberg H, Andersson DP, Qvisth V, Löfgren P, Rydén M, Thörne A, Wirén M, Palmér M, Thorell A, Toft E, Arner P. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity.. Diabetologia 2010 Dec;53(12):2496-503.
- Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, Basdevant A, Guerre-Millo M, Poitou C, Zucker JD, Bedossa P, Clément K. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss.. Diabetes 2010 Nov;59(11):2817-25.
- Gustafson B, Gogg S, Hedjazifar S, Jenndahl L, Hammarstedt A, Smith U. Inflammation and impaired adipogenesis in hypertrophic obesity in man.. Am J Physiol Endocrinol Metab 2009 Nov;297(5):E999-E1003.
- Gao H, Mejhert N, Fretz JA, Arner E, Lorente-Cebrián S, Ehrlund A, Dahlman-Wright K, Gong X, Strömblad S, Douagi I, Laurencikiene J, Dahlman I, Daub CO, Rydén M, Horowitz MC, Arner P. Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.. Cell Metab 2014 Jun 3;19(6):981-92.
- Guilherme A, Virbasius JV, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.. Nat Rev Mol Cell Biol 2008 May;9(5):367-77.
- Marycz K, Kornicka K, Szlapka-Kosarzewska J, Weiss C. Excessive Endoplasmic Reticulum Stress Correlates with Impaired Mitochondrial Dynamics, Mitophagy and Apoptosis, in Liver and Adipose Tissue, but Not in Muscles in EMS Horses.. Int J Mol Sci 2018 Jan 6;19(1).
- Morgan RA, Beck KR, Nixon M, Homer NZM, Crawford AA, Melchers D, Houtman R, Meijer OC, Stomby A, Anderson AJ, Upreti R, Stimson RH, Olsson T, Michoel T, Cohain A, Ruusalepp A, Schadt EE, Björkegren JLM, Andrew R, Kenyon CJ, Hadoke PWF, Odermatt A, Keen JA, Walker BR. Carbonyl reductase 1 catalyzes 20β-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity.. Sci Rep 2017 Sep 6;7(1):10633.
- Elzinga S, Wood P, Adams AA. Plasma lipidomic and inflammatory cytokine profiles of horses with equine metabolic syndrome. J. Equine. Vet. Sci. 2016;40:49‐55.
- Buff PR, Dodds AC, Morrison CD, Whitley NC, McFadin EL, Daniel JA, Djiane J, Keisler DH. Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition.. J Anim Sci 2002 Nov;80(11):2942-8.
- 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.. J Vet Intern Med 2010 Jul-Aug;24(4):932-9.
- Basinska K, Marycz K, Śieszek A, Nicpoń J. The production and distribution of IL-6 and TNF-a in subcutaneous adipose tissue and their correlation with serum concentrations in Welsh ponies with equine metabolic syndrome.. J Vet Sci 2015;16(1):113-20.
- Ungru J, Blüher M, Coenen M, Raila J, Boston R, Vervuert I. Effects of body weight reduction on blood adipokines and subcutaneous adipose tissue adipokine mRNA expression profiles in obese ponies.. Vet Rec 2012 Nov 24;171(21):528.
- Vick MM, Adams AA, Murphy BA, Sessions DR, Horohov DW, Cook RF, Shelton BJ, Fitzgerald BP. Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse.. J Anim Sci 2007 May;85(5):1144-55.
- 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.. J Vet Intern Med 2013 Jan-Feb;27(1):157-63.
- Verboven K, Wouters K, Gaens K, Hansen D, Bijnen M, Wetzels S, Stehouwer CD, Goossens GH, Schalkwijk CG, Blaak EE, Jocken JW. Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans.. Sci Rep 2018 Mar 16;8(1):4677.
- Carroll CL, Huntington PJ. Body condition scoring and weight estimation of horses.. Equine Vet J 1988 Jan;20(1):41-5.
- Copas VE, Durham AE. Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction.. Equine Vet J 2012 Jul;44(4):440-3.
- Miller MA, Pardo ID, Jackson LP, Moore GE, Sojka JE. Correlation of pituitary histomorphometry with adrenocorticotrophic hormone response to domperidone administration in the diagnosis of equine pituitary pars intermedia dysfunction.. Vet Pathol 2008 Jan;45(1):26-38.
- Galarraga M, Campión J, Muñoz-Barrutia A, Boqué N, Moreno H, Martínez JA, Milagro F, Ortiz-de-Solórzano C. Adiposoft: automated software for the analysis of white adipose tissue cellularity in histological sections.. J Lipid Res 2012 Dec;53(12):2791-6.
- Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I, Guerre-Millo M, Poitou C, Basdevant A, Stich V, Viguerie N, Langin D, Bedossa P, Zucker JD, Clement K. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity.. Genome Biol 2008 Jan 21;9(1):R14.
- Bustin SA. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems.. J Mol Endocrinol 2002 Aug;29(1):23-39.
- Bambace C, Telesca M, Zoico E, Sepe A, Olioso D, Rossi A, Corzato F, Di Francesco V, Mazzucco A, Santini F, Zamboni M. Adiponectin gene expression and adipocyte diameter: a comparison between epicardial and subcutaneous adipose tissue in men.. Cardiovasc Pathol 2011 Sep-Oct;20(5):e153-6.
- Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.. J Clin Invest 2006 Jun;116(6):1494-505.
- Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity.. Diabetologia 2016 May;59(5):879-94.
- Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue.. J Clin Invest 2003 Dec;112(12):1796-808.
- Peterson KR, Cottam MA, Kennedy AJ, Hasty AH. Macrophage-Targeted Therapeutics for Metabolic Disease.. Trends Pharmacol Sci 2018 Jun;39(6):536-546.
- Bamford NJ, Potter SJ, Baskerville CL, Harris PA, Bailey SR. Effect of increased adiposity on insulin sensitivity and adipokine concentrations in different equine breeds adapted to cereal-rich or fat-rich meals.. Vet J 2016 Aug;214:14-20.
- Guo KY, Halo P, Leibel RL, Zhang Y. Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice.. Am J Physiol Regul Integr Comp Physiol 2004 Jul;287(1):R112-9.
- Grant RW, Vester Boler BM, Ridge TK, Graves TK, Swanson KS. Adipose tissue transcriptome changes during obesity development in female dogs.. Physiol Genomics 2011 Mar 29;43(6):295-307.
- Nicholson T, Church C, Baker DJ, Jones SW. The role of adipokines in skeletal muscle inflammation and insulin sensitivity.. J Inflamm (Lond) 2018;15:9.
- Montague CT, Prins JB, Sanders L, Zhang J, Sewter CP, Digby J, Byrne CD, O'Rahilly S. Depot-related gene expression in human subcutaneous and omental adipocytes.. Diabetes 1998 Sep;47(9):1384-91.
- Lefebvre AM, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, Vidal H. Depot-specific differences in adipose tissue gene expression in lean and obese subjects.. Diabetes 1998 Jan;47(1):98-103.
- Warnken T, Brehm R, Feige K, Huber K. Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.. Domest Anim Endocrinol 2017 Oct;61:17-26.
- Heinonen S, Saarinen L, Naukkarinen J, Rodríguez A, Frühbeck G, Hakkarainen A, Lundbom J, Lundbom N, Vuolteenaho K, Moilanen E, Arner P, Hautaniemi S, Suomalainen A, Kaprio J, Rissanen A, Pietiläinen KH. Adipocyte morphology and implications for metabolic derangements in acquired obesity.. Int J Obes (Lond) 2014 Nov;38(11):1423-31.
- Donato AJ, Henson GD, Hart CR, Layec G, Trinity JD, Bramwell RC, Enz RA, Morgan RG, Reihl KD, Hazra S, Walker AE, Richardson RS, Lesniewski LA. The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction.. J Physiol 2014 Sep 15;592(18):4083-96.
- Martin-Gimenez T, de Blas I, Aguilera-Tejero E, Diez de Castro E, Aguirre-Pascasio CN. Endocrine, morphometric, and ultrasonographic characterization of neck adiposity in Andalusian horses.. Domest Anim Endocrinol 2016 Jul;56:57-62.
Citations
This article has been cited 16 times.- Petrova V, Yonkova P, Simeonova G, Vachkova E. Horse serum potentiates cellular viability and improves indomethacin-induced adipogenesis in equine subcutaneous adipose-derived stem cells (ASCs). Int J Vet Sci Med 2023;11(1):94-105.
- Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine Metabolic Syndrome: A Complex Disease Influenced by Multifactorial Genetic Factors. Genes (Basel) 2023 Jul 27;14(8).
- Bourebaba L, Zyzak M, Sikora M, Serwotka-Suszczak A, Mularczyk M, Al Naem M, Marycz K. Sex Hormone-Binding Globulin (SHBG) Maintains Proper Equine Adipose-Derived Stromal Cells (ASCs)' Metabolic Functions and Negatively Regulates their Basal Adipogenic Potential. Stem Cell Rev Rep 2023 Jul 4;.
- Pratt-Phillips S, Munjizun A. Impacts of Adiposity on Exercise Performance in Horses. Animals (Basel) 2023 Feb 14;13(4).
- Kim HJ, Jang YS, Ha JW, Ra MJ, Jung SM, Yu JN, Kim K, Kim KH, Um SH. Bioactive Phytochemicals from Salix pseudolasiogyne Twigs: Anti-Adipogenic Effect of 2'-O-Acetylsalicortin in 3T3-L1 Cells. Int J Mol Sci 2022 Oct 9;23(19).
- Trachsel DS, Stage HJ, Rausch S, Trappe S, Söllig K, Sponder G, Merle R, Aschenbach JR, Gehlen H. Comparison of Sources and Methods for the Isolation of Equine Adipose Tissue-Derived Stromal/Stem Cells and Preliminary Results on Their Reaction to Incubation with 5-Azacytidine. Animals (Basel) 2022 Aug 11;12(16).
- Mularczyk M, Bourebaba N, Marycz K, Bourebaba L. Astaxanthin Carotenoid Modulates Oxidative Stress in Adipose-Derived Stromal Cells Isolated from Equine Metabolic Syndrome Affected Horses by Targeting Mitochondrial Biogenesis. Biomolecules 2022 Jul 27;12(8).
- Suagee-Bedore J, Shost N, Miller C, Grado L, Bechelli J. Age and Body Condition Influence the Post-Prandial Interleukin-1β Response to a High-Starch Meal in Horses. Animals (Basel) 2021 Nov 24;11(12).
- Delarocque J, Frers F, Huber K, Jung K, Feige K, Warnken T. Metabolic impact of weight variations in Icelandic horses. PeerJ 2021;9:e10764.
- Fitzgerald DM, Anderson ST, Sillence MN, de Laat MA. The cresty neck score is an independent predictor of insulin dysregulation in ponies. PLoS One 2019;14(7):e0220203.
- Daradics Z, Popescu M, Cătoi C, Mircean MV, Macri A, Mîrza O, Szakacs A, Daina S, Fetea F, Tripon MA, Lupșan AF, Bungărdean D, Călugăr A, Bora FD, Crecan CM. Forage Carbohydrate Profiles and Endocrine Morphometric Interactions in Traditionally Managed Horses from Romania. Life (Basel) 2025 Nov 6;15(11).
- Bourebaba N, Domagała J, Bourebaba L. Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation. BMC Vet Res 2025 Oct 21;21(1):620.
- Tomal A, Szłapka-Kosarzewska J, Mironiuk M, Michalak I, Marycz K. Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions improves insulin sensitivity and reduces systemic inflammation in equine metabolic affected horses. Front Endocrinol (Lausanne) 2024;15:1382844.
- Pratt-Phillips S. Effect of Exercise Conditioning on Countering the Effects of Obesity and Insulin Resistance in Horses-A Review. Animals (Basel) 2024 Feb 26;14(5).
- Nowicka B, Torres A, Polkowska I, Jackow-Nowicka J, Przewozny M, Jackow-Malinowska J. Concentrations of Selected Adipocytokines in the Blood Plasma in Proximal Suspensory Desmopathy of Horses, with a Focus on Their Physical Activity-A Pilot Study. Int J Mol Sci 2023 Dec 22;25(1).
- Bourebaba L, Kępska M, Qasem B, Zyzak M, Łyczko J, Klemens M, Mularczyk M, Marycz K. Sex hormone-binding globulin improves lipid metabolism and reduces inflammation in subcutaneous adipose tissue of metabolic syndrome-affected horses. Front Mol Biosci 2023;10:1214961.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists