FREE SHIPPING over $40
Horse Supplements USA English
Horse Supplements Canada EnglishSuppléments Équins Canada French
My Account
View Cart My Horses Track Orders Account Details My Subscriptions Update Address Payment Methods
Register/Login
0
Home/Equine Research Bank/Animals (Basel)/A Potential Role for Pro-Inflammatory Cytokines in the Devel...
Animals : an open access journal from MDPI2012; 2(2); 243-260; doi: 10.3390/ani2020243

A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses.

Abstract: Understanding the mechanisms involved in the development of insulin resistance in horses should enable development of effective treatment and prevention strategies. Current knowledge of these mechanisms is based upon research in obese humans and rodents, in which there is evidence that the increased production of pro-inflammatory cytokines by adipose tissue negatively influences insulin signaling in insulin-responsive tissues. In horses, plasma concentrations of the cytokine, tumor necrosis factor-α, have been positively correlated with body fatness and insulin resistance, leading to the hypothesis that inflammation may reduce insulin sensitivity in horses. However, little evidence has documented a tissue site of production and a direct link between inflammation and induction of insulin resistance has not been established. Several mechanisms are reviewed in this article, including the potential for macrophage infiltration, hyperinsulinemia, hypoxia, and lipopolysaccharide to increase pro-inflammatory cytokine production by adipose tissue of obese horses. Clearly defining the role of cytokines in reduced insulin sensitivity of horses will be a very important step in determining how obesity and insulin resistance are related.
Get Full Text
Publication Date: 2012-05-02 PubMed ID: 26486919PubMed Central: PMC4494330DOI: 10.3390/ani2020243Google 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.
LinkedIn
  • Journal Article
  • Review

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.

This study investigates the possible role of pro-inflammatory cytokines in the development of insulin resistance in horses, drawing parallels to existing research conducted on humans and rodents.

Overview of the Research

The research aims to understand the mechanisms which result in insulin resistance in horses in the hope of building effective treatment and prevention strategies. It is established based on previous research done on obese humans and rodents which have shown that an increase in pro-inflammatory cytokines disrupts insulin signaling in insulin-responsive tissues.

Correlation between Cytokines and Insulin Resistance in Horses

  • The researchers have found that in horses, the concentration of a specific cytokine, tumor necrosis factor-α (TNF- α), in the blood directly correlates with both, body fatness and insulin resistance.
  • This leads them to hypothesize that inflammation may have a role in reducing insulin sensitivity in horses.
  • However, they note that there has been little documented evidence to show which tissues produce these cytokines and also to establish a direct connection between inflammation and induction of insulin resistance.

Proposed Mechanisms

The article reviews several mechanisms, including:

  • The potential for macrophage infiltration into adipose tissue, which could in turn lead to increased production of cytokines.
  • The effects of hyperinsulinemia (excess insulin in the blood)—common in obese horses—on the production of cytokines.
  • The possibility that hypoxia (low oxygen levels), a condition often seen in obesity, might lead to more cytokine production.
  • The role of lipopolysaccharide, a component of bacterial cell walls, in increasing cytokine production.

Future Implications of the Study

Investigating these mechanisms and establishing cytokines’ definitive role in horses could pave the way to understanding how obesity and insulin resistance are associated. This knowledge could then potentially be applied in the development of treatments for insulin resistance (and related conditions) in both, horses and potentially in humans as well.

Cite This Article

APA
Suagee JK, Corl BA, Geor RJ. (2012). A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses. Animals (Basel), 2(2), 243-260. https://doi.org/10.3390/ani2020243

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 2
Issue: 2
Pages: 243-260

Researcher Affiliations

Suagee, Jessica K
  • Department of Dairy Science, Virginia Tech, Blacksburg, VA 24071, USA. jksuagee@vt.edu.
Corl, Benjamin A
  • Department of Dairy Science, Virginia Tech, Blacksburg, VA 24071, USA. bcorl@vt.edu.
Geor, Raymond J
  • Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA. geor@cvm.msu.edu.

References

This article includes 122 references
  1. Jeffcott LB, Field JR, McLean JG, O'Dea K. Glucose tolerance and insulin sensitivity in ponies and Standardbred horses.. Equine Vet J 1986 Mar;18(2):97-101.
    pubmed: 3516677doi: 10.1111/j.2042-3306.1986.tb03556.xgoogle scholar: lookup
  2. Carter RA, Treiber KH, Geor RJ, Douglass L, Harris PA. Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies.. Equine Vet J 2009 Feb;41(2):171-8.
    pubmed: 19418747doi: 10.2746/042516408x342975google scholar: lookup
  3. Treiber K, Carter R, Gay L, Williams C, Geor R. Inflammatory and redox status of ponies with a history of pasture-associated laminitis.. Vet Immunol Immunopathol 2009 Jun 15;129(3-4):216-20.
    pubmed: 19108899doi: 10.1016/j.vetimm.2008.11.004google scholar: lookup
  4. Frank N. Equine metabolic syndrome. J. Equine Vet. Sci. 2009;29:259u2013267.
  5. Geor RJ, Harris P. Dietary management of obesity and insulin resistance: countering risk for laminitis.. Vet Clin North Am Equine Pract 2009 Apr;25(1):51-65, vi.
    doi: 10.1016/j.cveq.2009.02.001pubmed: 19303550google scholar: lookup
  6. Asegaonkar SB, Marathe A, Tekade ML, Cherekar L, Bavikar J, Bardapurkar J, Ajay R. High-sensitivity C-reactive protein: a novel cardiovascular risk predictor in type 2 diabetics with normal lipid profile.. J Diabetes Complications 2011 Nov-Dec;25(6):368-70.
    doi: 10.1016/j.jdiacomp.2011.10.001pubmed: 22055258google scholar: lookup
  7. Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system?. Diabetologia 1998 Oct;41(10):1241-8.
    pubmed: 9794114doi: 10.1007/s001250051058google scholar: lookup
  8. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M. Metabolic syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study.. Int J Obes Relat Metab Disord 2003 Oct;27(10):1283-9.
    doi: 10.1038/sj.ijo.0802381pubmed: 14513078google scholar: lookup
  9. Chan JC, Cheung JC, Stehouwer CD, Emeis JJ, Tong PC, Ko GT, Yudkin JS. The central roles of obesity-associated dyslipidaemia, endothelial activation and cytokines in the Metabolic Syndrome--an analysis by structural equation modelling.. Int J Obes Relat Metab Disord 2002 Jul;26(7):994-1008.
    pubmed: 12080455doi: 10.1038/sj.ijo.0802017google scholar: lookup
  10. Schmidt MI, Duncan BB, Sharrett AR, Lindberg G, Savage PJ, Offenbacher S, Azambuja MI, Tracy RP, Heiss G. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.. Lancet 1999 May 15;353(9165):1649-52.
    pubmed: 10335783doi: 10.1016/s0140-6736(99)01046-6google scholar: lookup
  11. Cartier A, Lemieux I, Almu00e9ras N, Tremblay A, Bergeron J, Despru00e9s JP. Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men.. J Clin Endocrinol Metab 2008 May;93(5):1931-8.
    doi: 10.1210/jc.2007-2191pubmed: 18319319google scholar: lookup
  12. Catalu00e1n V, Gu00f3mez-Ambrosi J, Ramirez B, Rotellar F, Pastor C, Silva C, Rodru00edguez A, Gil MJ, Cienfuegos JA, Fru00fchbeck G. Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass.. Obes Surg 2007 Nov;17(11):1464-74.
    pubmed: 18219773doi: 10.1007/s11695-008-9424-zgoogle scholar: lookup
  13. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X.. Diabetologia 1997 Nov;40(11):1286-92.
    pubmed: 9389420doi: 10.1007/s001250050822google scholar: lookup
  14. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes.. Diabetes Care 2004 Mar;27(3):813-23.
    doi: 10.2337/diacare.27.3.813pubmed: 14988310google scholar: lookup
  15. 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.
    doi: 10.2527/jas.2006-673pubmed: 17264235google scholar: lookup
  16. Suagee JK, Burk AO, Quinn RW, Hartsock TG, Douglass LW. Effects of diet and weight gain on circulating tumour necrosis factor-u03b1 concentrations in Thoroughbred geldings.. J Anim Physiol Anim Nutr (Berl) 2011 Apr;95(2):161-70.
    doi: 10.1111/j.1439-0396.2010.01036.xpubmed: 20666861google scholar: lookup
  17. Holbrook TC, Tipton T, McFarlane D. Neutrophil and cytokine dysregulation in hyperinsulinemic obese horses.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):283-9.
    doi: 10.1016/j.vetimm.2011.11.013pubmed: 22169327google scholar: lookup
  18. Villaret A, Galitzky J, Decaunes P, Estu00e8ve D, Marques MA, Sengenu00e8s C, Chiotasso P, Tchkonia T, Lafontan M, Kirkland JL, Bouloumiu00e9 A. Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence.. Diabetes 2010 Nov;59(11):2755-63.
    doi: 10.2337/db10-0398pmc: PMC2963533pubmed: 20713685google scholar: lookup
  19. 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.
    doi: 10.1111/j.1939-1676.2010.0551.xpubmed: 20649750google scholar: lookup
  20. Fain JN, Bahouth SW, Madan AK. TNFalpha release by the nonfat cells of human adipose tissue.. Int J Obes Relat Metab Disord 2004 Apr;28(4):616-22.
    doi: 10.1038/sj.ijo.0802594pubmed: 14770194google scholar: lookup
  21. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.. J Clin Invest 2003 Dec;112(12):1821-30.
    pmc: PMC296998pubmed: 14679177doi: 10.1172/JCI19451google scholar: lookup
  22. Lumeng CN, Deyoung SM, Saltiel AR. Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins.. Am J Physiol Endocrinol Metab 2007 Jan;292(1):E166-74.
    pmc: PMC3888778pubmed: 16926380doi: 10.1152/ajpendo.00284.2006google scholar: lookup
  23. Vick MM, Murphy BA, Sessions DR, Reedy SE, Kennedy EL, Horohov DW, Cook RF, Fitzgerald BP. Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue.. Am J Vet Res 2008 Jan;69(1):130-9.
    doi: 10.2460/ajvr.69.1.130pubmed: 18167098google scholar: lookup
  24. DeFronzo RA. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis.. Neth J Med 1997 May;50(5):191-7.
    pubmed: 9175399doi: 10.1016/s0300-2977(97)00012-0google scholar: lookup
  25. Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation.. J Leukoc Biol 2005 Oct;78(4):819-35.
    doi: 10.1189/jlb.0505247pubmed: 16033812google scholar: lookup
  26. Kim TH, Choi SE, Ha ES, Jung JG, Han SJ, Kim HJ, Kim DJ, Kang Y, Lee KW. IL-6 induction of TLR-4 gene expression via STAT3 has an effect on insulin resistance in human skeletal muscle.. Acta Diabetol 2013 Apr;50(2):189-200.
    pubmed: 21293887doi: 10.1007/s00592-011-0259-zgoogle scholar: lookup
  27. Saghizadeh M, Ong JM, Garvey WT, Henry RR, Kern PA. The expression of TNF alpha by human muscle. Relationship to insulin resistance.. J Clin Invest 1996 Feb 15;97(4):1111-6.
    doi: 10.1172/JCI118504pmc: PMC507159pubmed: 8613535google scholar: lookup
  28. Torres SH, De Sanctis JB, de L Briceu00f1o M, Hernu00e1ndez N, Finol HJ. Inflammation and nitric oxide production in skeletal muscle of type 2 diabetic patients.. J Endocrinol 2004 Jun;181(3):419-27.
    doi: 10.1677/joe.0.1810419pubmed: 15171690google scholar: lookup
  29. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes.. J Clin Invest 2005 May;115(5):1111-9.
    pmc: PMC1087185pubmed: 15864338doi: 10.1172/JCI25102google scholar: lookup
  30. Tschu00f6p M, Thomas G. Fat fuels insulin resistance through Toll-like receptors.. Nat Med 2006 Dec;12(12):1359-61.
    pubmed: 17151692doi: 10.1038/nm1206-1359google scholar: lookup
  31. Boyd JH, Divangahi M, Yahiaoui L, Gvozdic D, Qureshi S, Petrof BJ. Toll-like receptors differentially regulate CC and CXC chemokines in skeletal muscle via NF-kappaB and calcineurin.. Infect Immun 2006 Dec;74(12):6829-38.
    pmc: PMC1698076pubmed: 16982839doi: 10.1128/IAI.00286-06google scholar: lookup
  32. Coletta DK, Balas B, Chavez AO, Baig M, Abdul-Ghani M, Kashyap SR, Folli F, Tripathy D, Mandarino LJ, Cornell JE, Defronzo RA, Jenkinson CP. Effect of acute physiological hyperinsulinemia on gene expression in human skeletal muscle in vivo.. Am J Physiol Endocrinol Metab 2008 May;294(5):E910-7.
    doi: 10.1152/ajpendo.00607.2007pmc: PMC3581328pubmed: 18334611google scholar: lookup
  33. Wearn JG, Suagee JK, Crisman MV, Corl BA, Hulver MW, Hodgson DR, Geor RJ, McCutcheon LJ. Effects of the insulin sensitizing drug, pioglitazone, and lipopolysaccharide administration on markers of systemic inflammation and clinical parameters in horses.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):42-9.
    doi: 10.1016/j.vetimm.2011.10.007pubmed: 22088672google scholar: lookup
  34. Suagee JK, Corl BA, Crisman MV, Hulver MW, McCutcheon LJ, Geor RJ. Effects of acute hyperinsulinemia on inflammatory proteins in horses.. Vet Immunol Immunopathol 2011 Aug 15;142(3-4):141-6.
    doi: 10.1016/j.vetimm.2011.05.001pubmed: 21621276google scholar: lookup
  35. 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.
    pmc: PMC296995pubmed: 14679176doi: 10.1172/JCI19246google scholar: lookup
  36. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue.. J Clin Invest 2003 Dec;112(12):1785-8.
    pmc: PMC297006pubmed: 14679172doi: 10.1172/JCI20514google scholar: lookup
  37. Burns T.A., Geor R.J., Mudge M.C., McCutcheon L.J., Belknap J. Characterization of adipose tissue macrophage infilitration in insulin-resistant and insulin-sensitive light breed horses; Proceedings of the 28th Annual Forum of the American College of Veterinary Internal Medicine; Anaheim, CA, USA. 9-12 June 2010.
  38. Do MS, Jeong HS, Choi BH, Hunter L, Langley S, Pazmany L, Trayhurn P. Inflammatory gene expression patterns revealed by DNA microarray analysis in TNF-alpha-treated SGBS human adipocytes.. Yonsei Med J 2006 Oct 31;47(5):729-36.
    pmc: PMC2687760pubmed: 17066518doi: 10.3349/ymj.2006.47.5.729google scholar: lookup
  39. 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.
    doi: 10.1172/JCI26498pmc: PMC1459069pubmed: 16691291google scholar: lookup
  40. Sartipy P, Loskutoff DJ. Expression profiling identifies genes that continue to respond to insulin in adipocytes made insulin-resistant by treatment with tumor necrosis factor-alpha.. J Biol Chem 2003 Dec 26;278(52):52298-306.
    pubmed: 14530283doi: 10.1074/jbc.M306922200google scholar: lookup
  41. Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, Kwon BS, Erickson KL, Yu R. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters.. Int J Obes (Lond) 2006 Sep;30(9):1347-55.
    pubmed: 16534530doi: 10.1038/sj.ijo.0803259google scholar: lookup
  42. Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects.. Int J Obes (Lond) 2005 Jan;29(1):146-50.
    pubmed: 15520826doi: 10.1038/sj.ijo.0802839google scholar: lookup
  43. Chen A, Mumick S, Zhang C, Lamb J, Dai H, Weingarth D, Mudgett J, Chen H, MacNeil DJ, Reitman ML, Qian S. Diet induction of monocyte chemoattractant protein-1 and its impact on obesity.. Obes Res 2005 Aug;13(8):1311-20.
    pubmed: 16129712doi: 10.1038/oby.2005.159google scholar: lookup
  44. Tateya S, Tamori Y, Kawaguchi T, Kanda H, Kasuga M. An increase in the circulating concentration of monocyte chemoattractant protein-1 elicits systemic insulin resistance irrespective of adipose tissue inflammation in mice.. Endocrinology 2010 Mar;151(3):971-9.
    pubmed: 20056828doi: 10.1210/en.2009-0926google scholar: lookup
  45. Fain JN, Madan AK. Regulation of monocyte chemoattractant protein 1 (MCP-1) release by explants of human visceral adipose tissue.. Int J Obes (Lond) 2005 Nov;29(11):1299-307.
    pubmed: 15997242doi: 10.1038/sj.ijo.0803032google scholar: lookup
  46. Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT.. J Clin Endocrinol Metab 2005 Apr;90(4):2282-9.
    doi: 10.1210/jc.2004-1696pubmed: 15671098google scholar: lookup
  47. Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes.. Mol Cell Endocrinol 2001 Apr 25;175(1-2):81-92.
    pubmed: 11325518doi: 10.1016/s0303-7207(01)00394-xgoogle scholar: lookup
  48. Vervuert I, Voigt K, Hollands T, Cuddeford D, Coenen M. Effect of feeding increasing quantities of starch on glycaemic and insulinaemic responses in healthy horses.. Vet J 2009 Oct;182(1):67-72.
    pubmed: 18558504doi: 10.1016/j.tvjl.2008.04.011google scholar: lookup
  49. Ruge T, Lockton JA, Renstrom F, Lystig T, Sukonina V, Svensson MK, Eriksson JW. Acute hyperinsulinemia raises plasma interleukin-6 in both nondiabetic and type 2 diabetes mellitus subjects, and this effect is inversely associated with body mass index.. Metabolism 2009 Jun;58(6):860-6.
    pubmed: 19375766doi: 10.1016/j.metabol.2009.02.010google scholar: lookup
  50. Siklova-Vitkova M, Polak J, Klimcakova E, Vrzalova J, Hejnova J, Kovacikova M, Kovacova Z, Bajzova M, Rossmeislova L, Hnevkovska Z, Langin D, Stich V. Effect of hyperinsulinemia and very-low-calorie diet on interstitial cytokine levels in subcutaneous adipose tissue of obese women.. Am J Physiol Endocrinol Metab 2009 Nov;297(5):E1154-61.
    doi: 10.1152/ajpendo.00086.2009pubmed: 19724021google scholar: lookup
  51. Hoffman RM, Boston RC, Stefanovski D, Kronfeld DS, Harris PA. Obesity and diet affect glucose dynamics and insulin sensitivity in Thoroughbred geldings.. J Anim Sci 2003 Sep;81(9):2333-42.
    pubmed: 12968709doi: 10.2527/2003.8192333xgoogle scholar: lookup
  52. Fasshauer M, Klein J, Lossner U, Paschke R. Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes.. Horm Metab Res 2003 Mar;35(3):147-52.
    doi: 10.1055/s-2003-39075pubmed: 12734774google scholar: lookup
  53. Vicennati V, Vottero A, Friedman C, Papanicolaou DA. Hormonal regulation of interleukin-6 production in human adipocytes.. Int J Obes Relat Metab Disord 2002 Jul;26(7):905-11.
    doi: 10.1038/sj.ijo.0802035pubmed: 12080442google scholar: lookup
  54. Dendorfer U, Oettgen P, Libermann TA. Interleukin-6 Gene Expression by Prostaglandins and Cyclic AMP Mediated by Multiple Regulatory Elements.. Am J Ther 1995 Sep;2(9):660-665.
    pubmed: 11854843doi: 10.1097/00045391-199509000-00014google scholar: lookup
  55. LaPensee CR, Hugo ER, Ben-Jonathan N. Insulin stimulates interleukin-6 expression and release in LS14 human adipocytes through multiple signaling pathways.. Endocrinology 2008 Nov;149(11):5415-22.
    pmc: PMC2584585pubmed: 18617614doi: 10.1210/en.2008-0549google scholar: lookup
  56. Kabon B, Nagele A, Reddy D, Eagon C, Fleshman JW, Sessler DI, Kurz A. Obesity decreases perioperative tissue oxygenation.. Anesthesiology 2004 Feb;100(2):274-80.
    pmc: PMC1395476pubmed: 14739800doi: 10.1097/00000542-200402000-00015google scholar: lookup
  57. Karhausen J, Haase VH, Colgan SP. Inflammatory hypoxia: role of hypoxia-inducible factor.. Cell Cycle 2005 Feb;4(2):256-8.
    pubmed: 15655360
  58. Lolmu00e8de K, Durand de Saint Front V, Galitzky J, Lafontan M, Bouloumiu00e9 A. Effects of hypoxia on the expression of proangiogenic factors in differentiated 3T3-F442A adipocytes.. Int J Obes Relat Metab Disord 2003 Oct;27(10):1187-95.
    pubmed: 14513066doi: 10.1038/sj.ijo.0802407google scholar: lookup
  59. Thurlby PL, Trayhurn P. Regional blood flow in genetically obese (ob/ob) mice. The importance of brown adipose tissue to the reduced energy expenditure on non-shivering thermogenesis.. Pflugers Arch 1980 Jun;385(3):193-201.
    doi: 10.1007/BF00647457pubmed: 7190682google scholar: lookup
  60. Karpe F, Fielding BA, Ilic V, Macdonald IA, Summers LK, Frayn KN. Impaired postprandial adipose tissue blood flow response is related to aspects of insulin sensitivity.. Diabetes 2002 Aug;51(8):2467-73.
    pubmed: 12145159doi: 10.2337/diabetes.51.8.2467google scholar: lookup
  61. Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice.. Am J Physiol Endocrinol Metab 2007 Oct;293(4):E1118-28.
    doi: 10.1152/ajpendo.00435.2007pubmed: 17666485google scholar: lookup
  62. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration.. Int J Obes (Lond) 2008 Mar;32(3):451-63.
    doi: 10.1038/sj.ijo.0803744pubmed: 17895881google scholar: lookup
  63. O'Rourke RW, White AE, Metcalf MD, Olivas AS, Mitra P, Larison WG, Cheang EC, Varlamov O, Corless CL, Roberts CT Jr, Marks DL. Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells.. Diabetologia 2011 Jun;54(6):1480-90.
    pmc: PMC3159546pubmed: 21400042doi: 10.1007/s00125-011-2103-ygoogle scholar: lookup
  64. Semenza GL. Life with oxygen.. Science 2007 Oct 5;318(5847):62-4.
    pubmed: 17916722doi: 10.1126/science.1147949google scholar: lookup
  65. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.. Science 2001 Apr 20;292(5516):464-8.
    pubmed: 11292862doi: 10.1126/science.1059817google scholar: lookup
  66. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.. Science 2001 Apr 20;292(5516):468-72.
    pubmed: 11292861doi: 10.1126/science.1059796google scholar: lookup
  67. Semenza GL. Targeting HIF-1 for cancer therapy.. Nat Rev Cancer 2003 Oct;3(10):721-32.
    pubmed: 13130303doi: 10.1038/nrc1187google scholar: lookup
  68. Rocha S. Gene regulation under low oxygen: holding your breath for transcription.. Trends Biochem Sci 2007 Aug;32(8):389-97.
    pubmed: 17624786doi: 10.1016/j.tibs.2007.06.005google scholar: lookup
  69. Wang B, Wood IS, Trayhurn P. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes.. Pflugers Arch 2007 Dec;455(3):479-92.
    pmc: PMC2040175pubmed: 17609976doi: 10.1007/s00424-007-0301-8google scholar: lookup
  70. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumiu00e9 A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clu00e9ment K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss.. Diabetes 2005 Aug;54(8):2277-86.
    pubmed: 16046292doi: 10.2337/diabetes.54.8.2277google scholar: lookup
  71. Cummins EP, Taylor CT. Hypoxia-responsive transcription factors.. Pflugers Arch 2005 Sep;450(6):363-71.
    pubmed: 16007431doi: 10.1007/s00424-005-1413-7google scholar: lookup
  72. Koong AC, Chen EY, Giaccia AJ. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues.. Cancer Res 1994 Mar 15;54(6):1425-30.
    pubmed: 8137243
  73. Cummins EP, Berra E, Comerford KM, Ginouves A, Fitzgerald KT, Seeballuck F, Godson C, Nielsen JE, Moynagh P, Pouyssegur J, Taylor CT. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity.. Proc Natl Acad Sci U S A 2006 Nov 28;103(48):18154-9.
    pmc: PMC1643842pubmed: 17114296doi: 10.1073/pnas.0602235103google scholar: lookup
  74. Belaiba RS, Bonello S, Zu00e4hringer C, Schmidt S, Hess J, Kietzmann T, Gu00f6rlach A. Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells.. Mol Biol Cell 2007 Dec;18(12):4691-7.
    pmc: PMC2096613pubmed: 17898080doi: 10.1091/mbc.e07-04-0391google scholar: lookup
  75. van Uden P, Kenneth NS, Rocha S. Regulation of hypoxia-inducible factor-1alpha by NF-kappaB.. Biochem J 2008 Jun 15;412(3):477-84.
    doi: 10.1042/BJ20080476pmc: PMC2474706pubmed: 18393939google scholar: lookup
  76. Swyers KL, Burk AO, Hartsock TG, Ungerfeld EM, Shelton JL. Effects of direct-fed microbial supplementation on digestibility and fermentation end-products in horses fed low- and high-starch concentrates.. J Anim Sci 2008 Oct;86(10):2596-608.
    pubmed: 18407981doi: 10.2527/jas.2007-0608google scholar: lookup
  77. Medina B, Girard ID, Jacotot E, Julliand V. Effect of a preparation of Saccharomyces cerevisiae on microbial profiles and fermentation patterns in the large intestine of horses fed a high fiber or a high starch diet.. J Anim Sci 2002 Oct;80(10):2600-9.
    pubmed: 12413082doi: 10.2527/2002.80102600xgoogle scholar: lookup
  78. Emmanuel DG, Madsen KL, Churchill TA, Dunn SM, Ametaj BN. Acidosis and lipopolysaccharide from Escherichia coli B:055 cause hyperpermeability of rumen and colon tissues.. J Dairy Sci 2007 Dec;90(12):5552-7.
    doi: 10.3168/jds.2007-0257pubmed: 18024746google scholar: lookup
  79. Khafipour E, Krause DO, Plaizier JC. A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation.. J Dairy Sci 2009 Mar;92(3):1060-70.
    doi: 10.3168/jds.2008-1389pubmed: 19233799google scholar: lookup
  80. Sprouse RF, Garner HE, Green EM. Plasma endotoxin levels in horses subjected to carbohydrate induced laminitis.. Equine Vet J 1987 Jan;19(1):25-8.
    pubmed: 3691456doi: 10.1111/j.2042-3306.1987.tb02571.xgoogle scholar: lookup
  81. Carroll CL, Hazard G, Coloe PJ, Hooper PT. Laminitis and possible enterotoxaemia associated with carbohydrate overload in mares.. Equine Vet J 1987 Jul;19(4):344-6.
    pubmed: 3622465doi: 10.1111/j.2042-3306.1987.tb01430.xgoogle scholar: lookup
  82. Prasse KW, Allen D Jr, Moore JN, Duncan A. Evaluation of coagulation and fibrinolysis during the prodromal stages of carbohydrate-induced acute laminitis in horses.. Am J Vet Res 1990 Dec;51(12):1950-5.
    pubmed: 2085221
  83. Budak MT, Orsini JA, Pollitt CC, Rubinstein NA. Gene expression in the lamellar dermis-epidermis during the developmental phase of carbohydrate overload-induced laminitis in the horse.. Vet Immunol Immunopathol 2009 Sep 15;131(1-2):86-96.
    pubmed: 19380162doi: 10.1016/j.vetimm.2009.03.019google scholar: lookup
  84. Tu00f3th F, Frank N, Chameroy KA, Bostont RC. Effects of endotoxaemia and carbohydrate overload on glucose and insulin dynamics and the development of laminitis in horses.. Equine Vet J 2009 Dec;41(9):852-8.
    doi: 10.2746/042516409X479027pubmed: 20383981google scholar: lookup
  85. Krueger AS, Kinden DA, Garner HE, Sprouse RF. Ultrastructural study of the equine cecum during onset of laminitis.. Am J Vet Res 1986 Aug;47(8):1804-12.
    pubmed: 3752692
  86. Bailey SR, Adair HS, Reinemeyer CR, Morgan SJ, Brooks AC, Longhofer SL, Elliott J. Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis.. Vet Immunol Immunopathol 2009 Jun 15;129(3-4):167-73.
    doi: 10.1016/j.vetimm.2008.11.009pubmed: 19091426google scholar: lookup
  87. Tu00f3th F, Frank N, Elliott SB, Geor RJ, Boston RC. Effects of an intravenous endotoxin challenge on glucose and insulin dynamics in horses.. Am J Vet Res 2008 Jan;69(1):82-8.
    pubmed: 18167091doi: 10.2460/ajvr.69.1.82google scholar: lookup
  88. Nieto JE, MacDonald MH, Braim AE, Aleman M. Effect of lipopolysaccharide infusion on gene expression of inflammatory cytokines in normal horses in vivo.. Equine Vet J 2009 Sep;41(7):717-9.
    doi: 10.2746/042516409X464780pubmed: 19927593google scholar: lookup
  89. Hermann GE, Holmes GM, Rogers RC. TNF(alpha) modulation of visceral and spinal sensory processing.. Curr Pharm Des 2005;11(11):1391-409.
    pubmed: 15853670doi: 10.2174/1381612053507828google scholar: lookup
  90. Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.. J Exp Med 1988 Mar 1;167(3):1211-27.
    pmc: PMC2188883pubmed: 3351436doi: 10.1084/jem.167.3.1211google scholar: lookup
  91. van Miert AS, van Duin CT, Wensing T. Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha.. J Vet Pharmacol Ther 1992 Dec;15(4):332-42.
    pubmed: 1487832doi: 10.1111/j.1365-2885.1992.tb01025.xgoogle scholar: lookup
  92. Benhariz M, Goulet O, Salas J, Colomb V, Ricour C. Energy cost of fever in children on total parenteral nutrition.. Clin Nutr 1997 Oct;16(5):251-5.
    pubmed: 16844604doi: 10.1016/s0261-5614(97)80037-4google scholar: lookup
  93. Maratou E, Dimitriadis G, Kollias A, Boutati E, Lambadiari V, Mitrou P, Raptis SA. Glucose transporter expression on the plasma membrane of resting and activated white blood cells.. Eur J Clin Invest 2007 Apr;37(4):282-90.
    pubmed: 17373964doi: 10.1111/j.1365-2362.2007.01786.xgoogle scholar: lookup
  94. Mu00e9szu00e1ros K, Bojta J, Bautista AP, Lang CH, Spitzer JJ. Glucose utilization by Kupffer cells, endothelial cells, and granulocytes in endotoxemic rat liver.. Am J Physiol 1991 Jan;260(1 Pt 1):G7-12.
    pubmed: 1987809doi: 10.1152/ajpgi.1991.260.1.G7google scholar: lookup
  95. Krogh-Madsen R, Mu00f8ller K, Dela F, Kronborg G, Jauffred S, Pedersen BK. Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans.. Am J Physiol Endocrinol Metab 2004 May;286(5):E766-72.
    doi: 10.1152/ajpendo.00468.2003pubmed: 14722028google scholar: lookup
  96. Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance.. Exp Clin Endocrinol Diabetes 1999;107(2):119-25.
    doi: 10.1055/s-0029-1212086pubmed: 10320052google scholar: lookup
  97. Hardardu00f3ttir I, Gru00fcnfeld C, Feingold KR. Effects of endotoxin and cytokines on lipid metabolism.. Curr Opin Lipidol 1994 Jun;5(3):207-15.
    doi: 10.1097/00041433-199405030-00008pubmed: 7952915google scholar: lookup
  98. Das UN. Is obesity an inflammatory condition?. Nutrition 2001 Nov-Dec;17(11-12):953-66.
    doi: 10.1016/S0899-9007(01)00672-4pubmed: 11744348google scholar: lookup
  99. Engstru00f6m G, Hedblad B, Stavenow L, Lind P, Janzon L, Lindgu00e4rde F. Inflammation-sensitive plasma proteins are associated with future weight gain.. Diabetes 2003 Aug;52(8):2097-101.
    pubmed: 12882928doi: 10.2337/diabetes.52.8.2097google scholar: lookup
  100. Festa A, D'Agostino R Jr, Howard G, Mykku00e4nen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).. Circulation 2000 Jul 4;102(1):42-7.
    pubmed: 10880413doi: 10.1161/01.cir.102.1.42google scholar: lookup
  101. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ.. J Clin Endocrinol Metab 2004 Jun;89(6):2548-56.
    doi: 10.1210/jc.2004-0395pubmed: 15181022google scholar: lookup
  102. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue.. Br J Nutr 2004 Sep;92(3):347-55.
    pubmed: 15469638doi: 10.1079/bjn20041213google scholar: lookup
  103. Vettor R, Milan G, Rossato M, Federspil G. Review article: adipocytokines and insulin resistance.. Aliment Pharmacol Ther 2005 Nov;22 Suppl 2:3-10.
    doi: 10.1111/j.1365-2036.2005.02587.xpubmed: 16225463google scholar: lookup
  104. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?. Arterioscler Thromb Vasc Biol 1999 Apr;19(4):972-8.
    doi: 10.1161/01.ATV.19.4.972pubmed: 10195925google scholar: lookup
  105. Stephens JM, Lee J, Pilch PF. Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction.. J Biol Chem 1997 Jan 10;272(2):971-6.
    pubmed: 8995390doi: 10.1074/jbc.272.2.971google scholar: lookup
  106. Hauner H, Petruschke T, Russ M, Ru00f6hrig K, Eckel J. Effects of tumour necrosis factor alpha (TNF alpha) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture.. Diabetologia 1995 Jul;38(7):764-71.
    pubmed: 7556976doi: 10.1007/s001250050350google scholar: lookup
  107. Ishizuka K, Usui I, Kanatani Y, Bukhari A, He J, Fujisaka S, Yamazaki Y, Suzuki H, Hiratani K, Ishiki M, Iwata M, Urakaze M, Haruta T, Kobayashi M. Chronic tumor necrosis factor-alpha treatment causes insulin resistance via insulin receptor substrate-1 serine phosphorylation and suppressor of cytokine signaling-3 induction in 3T3-L1 adipocytes.. Endocrinology 2007 Jun;148(6):2994-3003.
    pubmed: 17379643doi: 10.1210/en.2006-1702google scholar: lookup
  108. Bouzakri K, Zierath JR. MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-alpha-induced insulin resistance.. J Biol Chem 2007 Mar 16;282(11):7783-9.
    pubmed: 17227768doi: 10.1074/jbc.M608602200google scholar: lookup
  109. Jager J, Gru00e9meaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression.. Endocrinology 2007 Jan;148(1):241-51.
    pmc: PMC1971114pubmed: 17038556doi: 10.1210/en.2006-0692google scholar: lookup
  110. Lagathu C, Yvan-Charvet L, Bastard JP, Maachi M, Quignard-Boulangu00e9 A, Capeau J, Caron M. Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes.. Diabetologia 2006 Sep;49(9):2162-73.
    pubmed: 16865359doi: 10.1007/s00125-006-0335-zgoogle scholar: lookup
  111. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice.. Diabetes 2003 Nov;52(11):2784-9.
    pubmed: 14578297doi: 10.2337/diabetes.52.11.2784google scholar: lookup
  112. Lagathu C, Bastard JP, Auclair M, Maachi M, Capeau J, Caron M. Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone.. Biochem Biophys Res Commun 2003 Nov 14;311(2):372-9.
    doi: 10.1016/j.bbrc.2003.10.013pubmed: 14592424google scholar: lookup
  113. Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects.. J Biol Chem 2003 Nov 14;278(46):45777-84.
    pubmed: 12952969doi: 10.1074/jbc.M301977200google scholar: lookup
  114. Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro.. J Clin Endocrinol Metab 2002 May;87(5):2084-9.
    pubmed: 11994345doi: 10.1210/jcem.87.5.8450google scholar: lookup
  115. Pedersen BK, Akerstru00f6m TC, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism.. J Appl Physiol (1985) 2007 Sep;103(3):1093-8.
    doi: 10.1152/japplphysiol.00080.2007pubmed: 17347387google scholar: lookup
  116. Plomgaard P, Bouzakri K, Krogh-Madsen R, Mittendorfer B, Zierath JR, Pedersen BK. Tumor necrosis factor-alpha induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation.. Diabetes 2005 Oct;54(10):2939-45.
    pubmed: 16186396doi: 10.2337/diabetes.54.10.2939google scholar: lookup
  117. Begum N, Ragolia L. Effect of tumor necrosis factor-alpha on insulin action in cultured rat skeletal muscle cells.. Endocrinology 1996 Jun;137(6):2441-6.
    pubmed: 8641197doi: 10.1210/endo.137.6.8641197google scholar: lookup
  118. de Alvaro C, Teruel T, Hernandez R, Lorenzo M. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner.. J Biol Chem 2004 Apr 23;279(17):17070-8.
    pubmed: 14764603doi: 10.1074/jbc.M312021200google scholar: lookup
  119. Rosenzweig T, Braiman L, Bak A, Alt A, Kuroki T, Sampson SR. Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling.. Diabetes 2002 Jun;51(6):1921-30.
    pubmed: 12031982doi: 10.2337/diabetes.51.6.1921google scholar: lookup
  120. Grzelkowska-Kowalczyk K, Wieteska-Skrzeczyu0144ska W. Treatment with TNF-alpha and IFN-gamma alters the activation of SER/THR protein kinases and the metabolic response to IGF-I in mouse c2c12 myogenic cells.. Cell Mol Biol Lett 2010;15(1):13-31.
    doi: 10.2478/s11658-009-0033-1pmc: PMC6275934pubmed: 19685010google scholar: lookup
  121. Kim HJ, Higashimori T, Park SY, Choi H, Dong J, Kim YJ, Noh HL, Cho YR, Cline G, Kim YB, Kim JK. Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo.. Diabetes 2004 Apr;53(4):1060-7.
    doi: 10.2337/diabetes.53.4.1060pubmed: 15047622google scholar: lookup
  122. Seyoum B, Fite A, Abou-Samra AB. Effects of 3T3 adipocytes on interleukin-6 expression and insulin signaling in L6 skeletal muscle cells.. Biochem Biophys Res Commun 2011 Jun 24;410(1):13-8.
    doi: 10.1016/j.bbrc.2011.05.073pubmed: 21640704google scholar: lookup

Citations

This article has been cited 2 times.
  1. Pielok A, Ku0119pska M, Steczkiewicz Z, Grobosz S, Bourebaba L, Marycz K. Equine Hoof Progenitor Cells Display Increased Mitochondrial Metabolism and Adaptive Potential to a Highly Pro-Inflammatory Microenvironment.. Int J Mol Sci 2023 Jul 14;24(14).
    doi: 10.3390/ijms241411446pubmed: 37511204google scholar: lookup
  2. Basinska K, Marycz K, u015aieszek A, Nicpou0144 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.
    doi: 10.4142/jvs.2015.16.1.113pubmed: 25269712google scholar: lookup

Secure Payments

PayPal Visa Mastercard American Express

Satisfaction Guarantee

We offer a 60-day guarantee to ensure you are completely satisfied.

Fast & Free Shipping

We provide fast and free shipping on all orders over $40.

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