Effects of a docosahexaenoic acid–rich microalgae nutritional product on insulin sensitivity after prolonged dexamethasone treatment in healthy mature horses

Kristen M. Brennan Center for Animal Nutrigenomics and Applied Animal Nutrition, Alltech Inc, 3031 Catnip Hill Rd, Nicholasville, KY 40356.

Search for other papers by Kristen M. Brennan in
Current site
Google Scholar
PubMed
Close
 PhD
,
Daniel E. Graugnard Center for Animal Nutrigenomics and Applied Animal Nutrition, Alltech Inc, 3031 Catnip Hill Rd, Nicholasville, KY 40356.

Search for other papers by Daniel E. Graugnard in
Current site
Google Scholar
PubMed
Close
 PhD
,
Malinda L. Spry Center for Animal Nutrigenomics and Applied Animal Nutrition, Alltech Inc, 3031 Catnip Hill Rd, Nicholasville, KY 40356.

Search for other papers by Malinda L. Spry in
Current site
Google Scholar
PubMed
Close
 MS
,
Tammy Brewster-Barnes Department of Animal and Food Sciences, College of Agriculture, Food, and Environment, University of Kentucky, Lexington, KY 40546.

Search for other papers by Tammy Brewster-Barnes in
Current site
Google Scholar
PubMed
Close
 MS
,
Allison C. Smith Center for Animal Nutrigenomics and Applied Animal Nutrition, Alltech Inc, 3031 Catnip Hill Rd, Nicholasville, KY 40356.

Search for other papers by Allison C. Smith in
Current site
Google Scholar
PubMed
Close
 BS
,
Rachel E. Schaeffer Center for Animal Nutrigenomics and Applied Animal Nutrition, Alltech Inc, 3031 Catnip Hill Rd, Nicholasville, KY 40356.

Search for other papers by Rachel E. Schaeffer in
Current site
Google Scholar
PubMed
Close
 BS
, and
Kristine L. Urschel Department of Animal and Food Sciences, College of Agriculture, Food, and Environment, University of Kentucky, Lexington, KY 40546.

Search for other papers by Kristine L. Urschel in
Current site
Google Scholar
PubMed
Close
 PhD

Abstract

OBJECTIVE To determine effects of a microalgae nutritional product on insulin sensitivity in horses.

ANIMALS 8 healthy mature horses.

PROCEDURES Horses (n = 4/group) received a basal diet without (control diet) or with docosahexaenoic acid–rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet). On day 28, an isoglycemic hyperinsulinemic clamp procedure was performed. Horses then received dexamethasone (0.04 mg/kg/d) for 21 days. On day 49, the clamp procedure was repeated. After a 60-day washout, horses received the alternate diet, and procedures were repeated. Plasma fatty acid, glucose, and insulin concentrations and glucose and insulin dynamics during the clamp procedure were measured on days 28 and 49. Two estimates of insulin sensitivity (reciprocal of the square root of the insulin concentration and the modified insulin-to-glucose ratio for ponies) were calculated.

RESULTS Baseline glucose and insulin concentrations or measures of insulin sensitivity on day 28 did not differ between horses when fed the control diet or the basal diet plus microalgae meal. On day 49 (ie, after dexamethasone administration), the microalgae meal was associated with lower baseline insulin and glucose concentrations and an improved modified insulin-to-glucose ratio for ponies, compared with results for the control diet.

CONCLUSIONS AND CLINICAL RELEVANCE Although the microalgae meal had no effect on clamp variables following dexamethasone treatment, it was associated with improved plasma glucose and insulin concentrations and insulin sensitivity estimates. A role for microalgae in the nutritional management of insulin-resistant horses warrants investigation.

Abstract

OBJECTIVE To determine effects of a microalgae nutritional product on insulin sensitivity in horses.

ANIMALS 8 healthy mature horses.

PROCEDURES Horses (n = 4/group) received a basal diet without (control diet) or with docosahexaenoic acid–rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet). On day 28, an isoglycemic hyperinsulinemic clamp procedure was performed. Horses then received dexamethasone (0.04 mg/kg/d) for 21 days. On day 49, the clamp procedure was repeated. After a 60-day washout, horses received the alternate diet, and procedures were repeated. Plasma fatty acid, glucose, and insulin concentrations and glucose and insulin dynamics during the clamp procedure were measured on days 28 and 49. Two estimates of insulin sensitivity (reciprocal of the square root of the insulin concentration and the modified insulin-to-glucose ratio for ponies) were calculated.

RESULTS Baseline glucose and insulin concentrations or measures of insulin sensitivity on day 28 did not differ between horses when fed the control diet or the basal diet plus microalgae meal. On day 49 (ie, after dexamethasone administration), the microalgae meal was associated with lower baseline insulin and glucose concentrations and an improved modified insulin-to-glucose ratio for ponies, compared with results for the control diet.

CONCLUSIONS AND CLINICAL RELEVANCE Although the microalgae meal had no effect on clamp variables following dexamethasone treatment, it was associated with improved plasma glucose and insulin concentrations and insulin sensitivity estimates. A role for microalgae in the nutritional management of insulin-resistant horses warrants investigation.

Contributor Notes

Address correspondence to Dr. Brennan (Kbrennan@alltech.com).
  • 1. Kahn CR. Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism 1978; 27: 18931902.

    • Search Google Scholar
    • Export Citation
  • 2. Shanik MH, Xu Y, Skrha J, et al. Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care 2008; 31 (suppl 2): S262S268.

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

  • 4. Frank N. Equine metabolic syndrome. Vet Clin North Am Equine Pract 2011; 27: 7392.

  • 5. Luo J, Rizkalla SW, Boillot J, et al. Dietary (n-3) polyunsaturated fatty acids improve adipocyte insulin action and glucose metabolism in insulin-resistant rats: relation to membrane fatty acids. J Nutr 1996; 126: 19511958.

    • Search Google Scholar
    • Export Citation
  • 6. Pérez-Matute P, Pérez-Echarri N, Martínez JA, et al. Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr 2007; 97: 389398.

    • Search Google Scholar
    • Export Citation
  • 7. Lombardo YB, Hein G, Chicco A. Metabolic syndrome: effects of n-3 PUFAs on a model of dyslipidemia, insulin resistance and adiposity. Lipids 2007; 42: 427437.

    • Search Google Scholar
    • Export Citation
  • 8. Ghafoorunissa, Ibrahim A, Rajkumar L, et al. Dietary (n-3) long chain polyunsaturated fatty acids prevent sucrose-induced insulin resistance in rats. J Nutr 2005; 135: 26342638.

    • Search Google Scholar
    • Export Citation
  • 9. Winzell MS, Pacini G, Ahren B. Insulin secretion after dietary supplementation with conjugated linoleic acids and n-3 polyunsaturated fatty acids in normal and insulin-resistant mice. Am J Physiol Endocrinol Metab 2006; 290: E347E354.

    • Search Google Scholar
    • Export Citation
  • 10. Storlien LH, Jenkins AB, Chisholm DJ, et al. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes 1991; 40: 280289.

    • Search Google Scholar
    • Export Citation
  • 11. Vaughan RA, Garcia-Smith R, Bisoffi M, et al. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells. Lipids Health Dis 2012; 11: 142.

    • Search Google Scholar
    • Export Citation
  • 12. Wei HK, Zhou Y, Jiang S, et al. Feeding a DHA-enriched diet increases skeletal muscle protein synthesis in growing pigs: association with increased skeletal muscle insulin action and local mRNA expression of insulin-like growth factor 1. Br J Nutr 2013; 110: 671680.

    • Search Google Scholar
    • Export Citation
  • 13. Figueras M, Olivan M, Busquets S, et al. Effects of eicosapentaenoic acid (EPA) treatment on insulin sensitivity in an animal model of diabetes: improvement of the inflammatory status. Obesity (Silver Spring) 2011; 19: 362369.

    • Search Google Scholar
    • Export Citation
  • 14. Hess TM, Rexford J, Hansen DK, et al. Effects of omega-3 (n-3) fatty acid supplementation on insulin sensitivity in horses. J Equine Vet Sci 2013; 33: 446453.

    • Search Google Scholar
    • Export Citation
  • 15. Vervuert I, Klein S, Coenen M. Short-term effects of a moderate fish oil or soybean oil supplementation on postprandial glucose and insulin responses in healthy horses. Vet J 2010; 184: 162166.

    • Search Google Scholar
    • Export Citation
  • 16. Tiley HA, Geor RJ, McCutcheon LJ. Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. Am J Vet Res 2007; 68: 753759.

    • Search Google Scholar
    • Export Citation
  • 17. Tiley HA, Geor RJ, McCutcheon LJ. Effects of dexamethasone administration on insulin resistance and components of insulin signaling and glucose metabolism in equine skeletal muscle. Am J Vet Res 2008; 69: 5158.

    • Search Google Scholar
    • Export Citation
  • 18. Tappy L, Randin D, Vollenweider P, et al. Mechanisms of dexamethasone-induced insulin resistance in healthy humans. J Clin Endocrinol Metab 1994; 79: 10631069.

    • Search Google Scholar
    • Export Citation
  • 19. Schneiter P, Tappy L. Kinetics of dexamethasone-induced alterations of glucose metabolism in healthy humans. Am J Physiol 1998; 275: E806E813.

    • Search Google Scholar
    • Export Citation
  • 20. Brown PD, Badal S, Morrison S, et al. Acute impairment of insulin signalling by dexamethasone in primary cultured rat skeletal myocytes. Mol Cell Biochem 2007; 297: 171177.

    • Search Google Scholar
    • Export Citation
  • 21. National Research Council. Nutrient requirements of horses. 6th ed. Washington, DC: National Academies Press, 2007.

  • 22. Tóth F, Frank N, Geor RJ, et al. Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses. Am J Vet Res 2010; 71: 6068.

    • Search Google Scholar
    • Export Citation
  • 23. Ralston SL. Insulin and glucose regulation. Vet Clin North Am Equine Pract 2002; 18: 295304.

  • 24. Haffner JC, Eiler H, Hoffman RM, et al. Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses by using the combined intravenous glucose and insulin test. J Anim Sci 2009; 87: 131135.

    • Search Google Scholar
    • Export Citation
  • 25. Urschel KL, Escobar J, McCutcheon LJ, et al. Effects of the rate of insulin infusion during isoglycemic, hyperinsulinemic clamp procedures on measures of insulin action in healthy, mature Thoroughbred mares. Domest Anim Endocrinol 2014; 47: 8391.

    • Search Google Scholar
    • Export Citation
  • 26. O'Fallon JV, Busboom JR, Nelson ML, et al. A direct method for fatty acid methyl ester synthesis: application to wet meat tissues, oils, and feedstuffs. J Anim Sci 2007; 85: 15111521.

    • Search Google Scholar
    • Export Citation
  • 27. Pratt SE, Geor RJ, McCutcheon LJ. Repeatability of 2 methods for assessment of insulin sensitivity and glucose dynamics in horses. J Vet Intern Med 2005; 19: 883888.

    • Search Google Scholar
    • Export Citation
  • 28. Reimers TJ, Cowan RG, McCann JP, et al. Validation of a rapid solid-phase radioimmunoassay for canine, bovine, and equine insulin. Am J Vet Res 1982; 43: 12741278.

    • Search Google Scholar
    • Export Citation
  • 29. Tinworth KD, Wynn PC, Boston RC, et al. Evaluation of commercially available assays for the measurement of equine insulin. Domest Anim Endocrinol 2011; 41: 8190.

    • Search Google Scholar
    • Export Citation
  • 30. Brennan KM, Urschel KL. Recovery of insulin sensitivity in mature horses after a 3 week course of dexamethasone therapy. Equine Vet J 2014; 46: 718721.

    • Search Google Scholar
    • Export Citation
  • 31. Treiber KH, Kronfeld DS, Hess TM, et al. Use of proxies and reference quintiles obtained from minimal model analysis for determination of insulin sensitivity and pancreatic beta-cell responsiveness in horses. Am J Vet Res 2005; 66: 21142121.

    • Search Google Scholar
    • Export Citation
  • 32. Borer KE, Bailey SR, Menzies-Gow NJ, et al. Use of proxy measurements of insulin sensitivity and insulin secretory response to distinguish between normal and previously laminitic ponies. Equine Vet J 2012; 44: 444448.

    • Search Google Scholar
    • Export Citation
  • 33. Treiber KH, Kronfeld DS, Geor RJ. Insulin resistance in equids: possible role in laminitis. J Nutr 2006; 136: 2094S2098S.

  • 34. King SS, Abughazaleh AA, Webel SK, et al. Circulating fatty acid profiles in response to three levels of dietary omega-3 fatty acid supplementation in horses. J Anim Sci 2008; 86: 11141123.

    • Search Google Scholar
    • Export Citation
  • 35. Muniyappa R, Lee S, Chen H, et al. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294: E15E26.

    • Search Google Scholar
    • Export Citation
  • 36. Ferrannini E, Mari A. How to measure insulin sensitivity. J Hypertens 1998; 16: 895906.

  • 37. Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010; 142: 687698.

    • Search Google Scholar
    • Export Citation
  • 38. Lombardo YB, Chicco A, D'Alessandro ME, et al. Dietary fish oil normalize dyslipidemia and glucose intolerance with unchanged insulin levels in rats fed a high sucrose diet. Biochim Biophys Acta 1996; 1299: 175182.

    • Search Google Scholar
    • Export Citation
  • 39. Pighin D, Karabatas L, Rossi A, et al. Fish oil affects pancreatic fat storage, pyruvate dehydrogenase complex activity and insulin secretion in rats fed a sucrose-rich diet. J Nutr 2003; 133: 40954101.

    • Search Google Scholar
    • Export Citation
  • 40. Rossi AS, Lombardo YB, Lacorte JM, et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats. Am J Physiol Regul Integr Comp Physiol 2005; 289: R486R494.

    • Search Google Scholar
    • Export Citation
  • 41. Lombardo YB, Chicco AG. Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review. J Nutr Biochem 2006; 17: 113.

    • Search Google Scholar
    • Export Citation
  • 42. Shimura T, Miura T, Usami M, et al. Docosahexanoic acid (DHA) improved glucose and lipid metabolism in KK-Ay mice with genetic non-insulin-dependent diabetes mellitus (NIDDM). Biol Pharm Bull 1997; 20: 507510.

    • Search Google Scholar
    • Export Citation
  • 43. Bremer AA, Stanhope KL, Graham JL, et al. Fish oil supplementation ameliorates fructose-induced hypertriglyceridemia and insulin resistance in adult male rhesus macaques. J Nutr 2014; 144: 511.

    • Search Google Scholar
    • Export Citation
  • 44. Delarue J, Li CH, Cohen R, et al. Interaction of fish oil and a glucocorticoid on metabolic responses to an oral glucose load in healthy human subjects. Br J Nutr 2006; 95: 267272.

    • Search Google Scholar
    • Export Citation
  • 45. Delarue J, Couet C, Cohen R, et al. Effects of fish oil on metabolic responses to oral fructose and glucose loads in healthy humans. Am J Physiol 1996; 270: E353E362.

    • Search Google Scholar
    • Export Citation
  • 46. Kabir M, Skurnik G, Naour N, et al. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 2007; 86: 16701679.

    • Search Google Scholar
    • Export Citation
  • 47. Barre DE. The role of consumption of alpha-linolenic, eicosapentaenoic and docosahexaenoic acids in human metabolic syndrome and type 2 diabetes—a mini-review. J Oleo Sci 2007; 56: 319325.

    • Search Google Scholar
    • Export Citation
  • 48. Fedor D, Kelley DS. Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 2009; 12: 138146.

    • Search Google Scholar
    • Export Citation
  • 49. Mustad VA, Demichele S, Huang YS, et al. Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse. Metabolism 2006; 55: 13651374.

    • Search Google Scholar
    • Export Citation
  • 50. Vemuri M, Kelley DS, Mackey BE, et al. Docosahexaenoic acid (DHA) but not eicosapentaenoic acid (EPA) prevents trans-10, cis-12 conjugated linoleic acid (CLA)-induced insulin resistance in mice. Metab Syndr Relat Disord 2007; 5: 315322.

    • Search Google Scholar
    • Export Citation
  • 51. Field LM. Successful treatment of lipohypertrophic insulin lipodystrophy with liposuction surgery. J Am Acad Dermatol 1988; 19: 570.

  • 52. Grunfeld C, Baird KL, Kahn CR. Maintenance of 3T3–L1 cells in culture media containing saturated fatty acids decreases insulin binding and insulin action. Biochem Biophys Res Commun 1981; 103: 219226.

    • Search Google Scholar
    • Export Citation
  • 53. Borkman M, Storlien LH, Pan DA, et al. The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. N Engl J Med 1993; 328: 238244.

    • Search Google Scholar
    • Export Citation

Advertisement