• 1. Chandler M, Cunningham S, Lund EM, et al. Obesity and associated comorbidities in people and companion animals: a one health perspective. J Comp Pathol 2017;156:296309.

    • Search Google Scholar
    • Export Citation
  • 2. Chandler ML. Impact of obesity on cardiopulmonary disease. Vet Clin North Am Small Anim Pract 2016;46:817830.

  • 3. Johnson PJ, Wiedmeyer CE, Messer NT, et al. Medical implications of obesity in horses—lessons for human obesity. J Diabetes Sci Technol 2009;3:163174.

    • Search Google Scholar
    • Export Citation
  • 4. Teixeira TF, Collado MC, Ferreira CL, et al. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res 2012;32:637647.

    • Search Google Scholar
    • Export Citation
  • 5. Geor RJ, Harris P. Dietary management of obesity and insulin resistance: countering risk for laminitis. Vet Clin North Am Equine Pract 2009;25:5165 (vi.).

    • Search Google Scholar
    • Export Citation
  • 6. Morris DD. Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis. J Vet Intern Med 1991;5:167181.

    • Search Google Scholar
    • Export Citation
  • 7. Moreno-Navarrete JM, Sabater M, Ortega F, et al. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS One 2012;7:e37160.

    • Search Google Scholar
    • Export Citation
  • 8. Gummesson A, Carlsson LM, Storlien LH, et al. Intestinal permeability is associated with visceral adiposity in healthy women. Obesity (Silver Spring) 2011;19:22802282.

    • Search Google Scholar
    • Export Citation
  • 9. Amar J, Chabo C, Waget A, et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med 2011;3:559572.

    • Search Google Scholar
    • Export Citation
  • 10. Ferraris RP, Vinnakota RR. Intestinal nutrient transport in genetically obese mice. Am J Clin Nutr 1995;62:540546.

  • 11. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57:14701481.

    • Search Google Scholar
    • Export Citation
  • 12. Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009;58:10911103.

    • Search Google Scholar
    • Export Citation
  • 13. Brun P, Castagliuolo I, Di Leo V, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2007;292:G518G525.

    • Search Google Scholar
    • Export Citation
  • 14. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab 2004;89:25832589.

  • 15. Schmidt FM, Weschenfelder J, Sander C, et al. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS One 2015;10:e0121971.

    • Search Google Scholar
    • Export Citation
  • 16. Mirhafez SR, Pasdar A, Avan A, et al. Cytokine and growth factor profiling in patients with the metabolic syndrome. Br J Nutr 2015;113:19111919.

    • Search Google Scholar
    • Export Citation
  • 17. Pirola L, Ferraz JC. Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity. World J Biol Chem 2017;8:120128.

    • Search Google Scholar
    • Export Citation
  • 18. Basinska K, Marycz K, Sieszek A, et al. The production and distribution of IL-6 and TNF-α in subcutaneous adipose tissue and their correlation with serum concentrations in Welsh ponies with equine metabolic syndrome. J Vet Sci 2015;16:113120.

    • Search Google Scholar
    • Export Citation
  • 19. Vick MM, Adams AA, Murphy BA, et al. Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse. J Anim Sci 2007;85:11441155.

    • Search Google Scholar
    • Export Citation
  • 20. Tadros EM, Frank N, Donnell RL. Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion. Am J Vet Res 2013;74:10101019.

    • Search Google Scholar
    • Export Citation
  • 21. Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 2010;314:116.

    • Search Google Scholar
    • Export Citation
  • 22. Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:17961808.

    • Search Google Scholar
    • Export Citation
  • 23. Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:18211830.

    • Search Google Scholar
    • Export Citation
  • 24. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56:17611772.

  • 25. Henneke DR, Potter GD, Kreider JL, et al. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J 1983;15:371372.

    • Search Google Scholar
    • Export Citation
  • 26. Schuver A, Frank N, Chameroy KA, et al. Assessment of insulin and glucose dynamics by using an oral sugar test in horses. J Equine Vet Sci 2014;34:465470.

    • Search Google Scholar
    • Export Citation
  • 27. Jacob SI, Geor RJ, Weber PSD, et al. Effect of age and dietary carbohydrate profiles on glucose and insulin dynamics in horses. Equine Vet J 2018;50:249254.

    • Search Google Scholar
    • Export Citation
  • 28. Equine Endocrinology Group. Recommendations for the diagnosis and treatment of equine metabolic syndrome (EMS). North Grafton, Mass: Tufts University, 2018.

    • Search Google Scholar
    • Export Citation
  • 29. Cook VL, Jones Shults J, McDowell M, et al. Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine. Equine Vet J 2008;40:353357.

    • Search Google Scholar
    • Export Citation
  • 30. Cook VL, Meyer CT, Campbell NB, et al. Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum. Am J Vet Res 2009;70:9921000.

    • Search Google Scholar
    • Export Citation
  • 31. Van Hoogmoed L, Snyder JR, Pascoe JR, et al. Use of pelvic flexure biopsies to predict survival after large colon torsion in horses. Vet Surg 2000;29:572577.

    • Search Google Scholar
    • Export Citation
  • 32. Shen L, Weber CR, Raleigh DR, et al. Tight junction pore and leak pathways: a dynamic duo. Annu Rev Physiol 2011;73:283309.

  • 33. Frizzell RA, Schultz SG. Ionic conductances of extracellular shunt pathway in rabbit ileum. Influence of shunt on transmural sodium transport and electrical potential differences. J Gen Physiol 1972;59:318346.

    • Search Google Scholar
    • Export Citation
  • 34. Okada Y, Irimajiri A, Inouye A. Electrical properties and active solute transport in rat small intestine. II. Conductive properties of transepithelial routes. J Membr Biol 1977;31:221232.

    • Search Google Scholar
    • Export Citation
  • 35. Rose RC, Schultz SG. Studies on the electrical potential profile across rabbit ileum. Effects of sugars and amino acids on transmural and transmucosal electrical potential differences. J Gen Physiol 1971;57:639663.

    • Search Google Scholar
    • Export Citation
  • 36. Gookin JL, Galanko JA, Blikslager AT, et al. PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum. Am J Physiol Gastrointest Liver Physiol 2003;285:G967G979.

    • Search Google Scholar
    • Export Citation
  • 37. Bauck AG, Grosche A, Morton AJ, et al. Effect of lidocaine on inflammation in equine jejunum subjected to manipulation only and remote to intestinal segments subjected to ischemia. Am J Vet Res 2017;78:977989.

    • Search Google Scholar
    • Export Citation
  • 38. Van Itallie CM, Anderson JM. Claudins and epithelial paracellular transport. Annu Rev Physiol 2006;68:403429.

  • 39. Oshima T, Miwa H. Gastrointestinal mucosal barrier function and diseases. J Gastroenterol 2016;51:768778.

  • 40. Little D, Brown SA, Campbell NB, et al. Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum. Am J Vet Res 2007;68:614624.

    • Search Google Scholar
    • Export Citation
  • 41. Watson CJ, Hoare CJ, Garrod DR, et al. Interferon-gamma selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores. J Cell Sci 2005;118:52215230.

    • Search Google Scholar
    • Export Citation
  • 42. Elzinga SE, Weese JS, Adams AA. Comparison of the fecal microbiota in horses with equine metabolic syndrome and metabolically normal controls fed a similar all-forage diet. J Equine Vet Sci 2016;44:916.

    • Search Google Scholar
    • Export Citation
  • 43. Morrison PK, Newbold CJ, Jones E, et al. The equine gastrointestinal microbiome: impacts of age and obesity. Front Microbiol 2018;9:30173020.

    • Search Google Scholar
    • Export Citation
  • 44. Biddle AS, Tomb J, Fan Z. Microbiome and blood analyte differences point to community and metabolic signatures in lean and obese horses. Front Vet Sci 2018;5:225.

    • Search Google Scholar
    • Export Citation
  • 45. Mshelia ES, Adamu L, Wakil Y, et al. The association between gut microbiome, sex age and body condition scores in horses in Maiduguri and its envrions. Microb Pathog 2018;118:8186.

    • Search Google Scholar
    • Export Citation
  • 46. Ericsson AC, Johnson PJ, Lopes MA, et al. A microbiological map of the healthy equine gastrointestinal tract. PLoS One 2016;11:117.

  • 47. Cox AJ, West NP, Cripps AW. Obesity, inflammation, and the gut microbiota. Lancet Diabetes Endocrinol 2015;3:207215.

  • 48. Upadhyay J, Farr O, Perakakis N, et al. Obesity as a disease. Med Clin North Am 2018;102:1333.

  • 49. Sahakyan KR, Somers VK, Rodriguez-Escudero JP, et al. Normal-weight central obesity: implications for total and cardiovascular mortality. Ann Intern Med 2015;163:827835.

    • Search Google Scholar
    • Export Citation
  • 50. Yam PS, Butowski CF, Chitty JL, et al. Impact of canine overweight and obesity on health-related quality of life. Prev Vet Med 2016;127:6469.

    • Search Google Scholar
    • Export Citation
  • 51. Clark M, Hoenig M. Metabolic effects of obesity and its interaction with endocrine diseases. Vet Clin North Am Small Anim Pract 2016;46:797815.

    • Search Google Scholar
    • Export Citation
  • 52. Packer MJ, German AJ, Hunter L, et al. Adipose tissue-derived adiponectin expression is significantly associated with increased post operative mortality in horses undergoing emergency abdominal surgery. Equine Vet J Suppl 2011;39:2633.

    • Search Google Scholar
    • Export Citation
  • 53. Kealy RD, Lawler DF, Ballam JM, et al. Five-year longitudinal study on limited food consumption and development of osteoarthritis in coxofemoral joints of dogs. J Am Vet Med Assoc 1997;210:222225.

    • Search Google Scholar
    • Export Citation
  • 54. Bach JF, Rozanski EA, Bedenice D, et al. Association of expiratory airway dysfunction with marked obesity in healthy adult dogs. Am J Vet Res 2007;68:670675.

    • Search Google Scholar
    • Export Citation
  • 55. Manens J, Bolognin M, Bernaerts F, et al. Effects of obesity on lung function and airway reactivity in healthy dogs. Vet J 2012;193:217221.

    • Search Google Scholar
    • Export Citation
  • 56. Gregory SP. Developments in the understanding of the pathophysiology of urethral sphincter mechanism in competence in the bitch. Br Vet J 1994;150:135150.

    • Search Google Scholar
    • Export Citation
  • 57. Potter SJ, Bamford NJ, Harris PA, et al. Incidence of laminitis and survey of dietary and management practices in pleasure horses and ponies in south-eastern Australia. Aust Vet J 2017;95:370374.

    • Search Google Scholar
    • Export Citation
  • 58. Frank N, Tadros EM. Insulin dysregulation. Equine Vet J 2014;46:103112.

  • 59. Frank N, Geor RJ, Bailey SR, et al. Equine metabolic syndrome. J Vet Intern Med 2010;24:467475.

  • 60. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559563.

  • 61. Dunbar LK, Mielnicki KA, Dembek KA, et al. Evaluation of four diagnostic tests for insulin dysregulation in adult light-breed horses. J Vet Intern Med 2016;30:885891.

    • Search Google Scholar
    • Export Citation
  • 62. Smith S, Harris PA, Menzies-Gow NJ. Comparison of the in-feed glucose test and the oral sugar test. Equine Vet J 2016;48:224227.

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Effect of body condition on intestinal permeability in horses

Jamie J. Kopper DVM, PhD1, Jennifer L. Travers DVM, JD1, Harold C. Schott II DVM, PhD1, and Vanessa L. Cook VetMD, PhD1
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  • 1 1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.

Abstract

OBJECTIVE

To investigate effects of body condition on permeability of intestinal mucosa in horses.

ANIMALS

13 horses (7 obese and 6 lean) from 8 to 15 years of age.

PROCEDURES

Body condition score was assessed, and an oral sugar test (OST) was performed to evaluate glucose and insulin dynamics. Horses were allowed a 2-week diet acclimation period and were then euthanized. Tissue samples were collected from the jejunum, ileum, cecum, pelvic flexure, right dorsal colon, and rectum. Mucosal permeability was assessed by measuring transepithelial resistance and lipopolysaccharide (LPS) flux across tissue samples mounted in Ussing chambers.

RESULTS

5 obese horses and 1 lean horse had evidence of insulin dysregulation, whereas 1 obese and 5 lean horses had no abnormalities in results of the OST. Results for the OST were not available for 1 obese horse. Mucosal transepithelial resistance did not differ in any intestinal segment between obese and lean horses. Obese horses had a significantly higher LPS flux across jejunal mucosa, compared with results for lean horses, but there were no significant differences between obese and lean horses for other intestinal segments.

CONCLUSIONS AND CLINICAL RELEVANCE

Obese horses may have had greater paracellular mucosal permeability of jejunal mucosa to LPS, compared with that for lean horses. This finding was consistent with data for the gastrointestinal mucosa of humans and mice and supported the hypothesis that obese horses may be at higher risk from chronic exposure to increased amounts of LPS, compared with the risk for lean horses.

Contributor Notes

Dr. Kopper's present address is Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

Address correspondence to Dr. Kopper (Jamie.kopper@wsu.edu).