Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This study examines the relationship between obesity, hyperinsulinemia (an excess of insulin in the blood), and oxidative stress in horses’ skeletal muscle. Results indicate that while obesity – tracked via body condition scores – did correlate with increased antioxidative responses in the muscles, this did not appear to be a central factor in the development of hyperinsulinemia.
Study Design and Hypothesis
- The research is centered around the mechanism of obesity-associated insulin dysregulation in horses, a topic that remains unclear. The researchers believed that oxidative stress in skeletal muscle might be associated with obesity-associated hyperinsulinemia.
The subjects and methods used
- The experiment involved 35 light breed horses with body condition scores (BCS) ranging from 3/9 to 9/9. The sample included obese horses both with normal insulin levels and raised insulin levels.
- Scientists performed skeletal muscle biopsies on these horses, investigating markers of oxidative stress, including oxidative damage, mitochondrial function, and antioxidant capacity.
Evaluation and Analysis
- A Spearman’s rank correlation coefficient was used to determine the relationship between markers of oxidative stress and Body Condition Scores (BCS).
- In addition, they compared markers of antioxidant capacity and oxidative damage among the lean normoinsulinemic (L-NI) horses, obese normoinsulinemic (O-NI) horses, and obese hyperinsulinemic (O-HI) horses.
Key Findings
- There was an increase in gene expression of a mitochondrial protein (ERRα), responsible for mitochondrial biogenesis, and increased antioxidant enzyme (TotSOD) activity as BCS increased.
- When the groups were compared, the activity of TotSOD was higher, and protein carbonyls, a marker of oxidative damage, was lower in the O-HI compared to L-NI horses.
- These data suggest that a protective antioxidant response occurred in the muscle of obese horses. However, the study concluded that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.
Therefore, these findings imply that while obesity stimulates an antioxidant response in the muscle of horses, this process may not be central in creating the condition of excessive insulin in the bloodstream. This result helps to eliminate one possible mechanism of obesity-associated insulin dysregulation in horses.
Cite This Article
Publication
Researcher Affiliations
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA (Banse, McFarlane); Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank); Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta T2N 4Z6 (Kwong).
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA (Banse, McFarlane); Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank); Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta T2N 4Z6 (Kwong).
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA (Banse, McFarlane); Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank); Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta T2N 4Z6 (Kwong).
- Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA (Banse, McFarlane); Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank); Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta T2N 4Z6 (Kwong).
MeSH Terms
- Animals
- Biomarkers
- Body Composition
- Horse Diseases / metabolism
- Horses
- Hyperinsulinism / etiology
- Hyperinsulinism / veterinary
- Muscle, Skeletal / metabolism
- Obesity / veterinary
- Oxidative Stress / physiology
References
- Thatcher CD, Pleasant RS, Geor RJ, Elvinger F. Prevalence of overconditioning in mature horses in southwest Virginia during the summer.. J Vet Intern Med 2012 Nov-Dec;26(6):1413-8.
- Stephenson HM, Green MJ, Freeman SL. Prevalence of obesity in a population of horses in the UK.. Vet Rec 2011 Feb 5;168(5):131.
- Wyse CA, McNie KA, Tannahill VJ, Murray JK, Love S. Prevalence of obesity in riding horses in Scotland.. Vet Rec 2008 May 3;162(18):590-1.
- 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.
- Muno JD. Prevalence, risk factors and seasonality of plasma insulin concentrations in normal horses in central Ohio.. 2009.
- Karikoski NP, Horn I, McGowan TW, McGowan CM. The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital.. Domest Anim Endocrinol 2011 Oct;41(3):111-7.
- Ingram KH, Hill H, Moellering DR, Hill BG, Lara-Castro C, Newcomer B, Brandon LJ, Ingalls CP, Penumetcha M, Rupp JC, Garvey WT. Skeletal muscle lipid peroxidation and insulin resistance in humans.. J Clin Endocrinol Metab 2012 Jul;97(7):E1182-6.
- Poelkens F, Lammers G, Pardoel EM, Tack CJ, Hopman MT. Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.. Exp Physiol 2013 Oct;98(10):1485-94.
- Coen PM, Hames KC, Leachman EM, DeLany JP, Ritov VB, Menshikova EV, Dubé JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity.. Obesity (Silver Spring) 2013 Nov;21(11):2362-71.
- Vinayagamoorthi R, Bobby Z, Sridhar MG. Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance.. J Endocrinol 2008 May;197(2):287-96.
- Hsieh CJ, Weng SW, Liou CW, Lin TK, Chen JB, Tiao MM, Hung YT, Chen IY, Huang WT, Wang PW. Tissue-specific differences in mitochondrial DNA content in type 2 diabetes.. Diabetes Res Clin Pract 2011 Apr;92(1):106-10.
- Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents.. J Clin Invest 2005 Dec;115(12):3587-93.
- Phielix E, Schrauwen-Hinderling VB, Mensink M, Lenaers E, Meex R, Hoeks J, Kooi ME, Moonen-Kornips E, Sels JP, Hesselink MK, Schrauwen P. Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients.. Diabetes 2008 Nov;57(11):2943-9.
- Jheng HF, Tsai PJ, Guo SM, Kuo LH, Chang CS, Su IJ, Chang CR, Tsai YS. Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle.. Mol Cell Biol 2012 Jan;32(2):309-19.
- Sebastián D, Hernández-Alvarez MI, Segalés J, Sorianello E, Muñoz JP, Sala D, Waget A, Liesa M, Paz JC, Gopalacharyulu P, Orešič M, Pich S, Burcelin R, Palacín M, Zorzano A. Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis.. Proc Natl Acad Sci U S A 2012 Apr 3;109(14):5523-8.
- Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A. The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis.. Proc Natl Acad Sci U S A 2004 Apr 27;101(17):6472-7.
- Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.. Cell 1999 Jul 9;98(1):115-24.
- Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance.. Am J Clin Nutr 1993 May;57(5 Suppl):715S-724S; discussion 724S-725S.
- Kalyanaraman B, Darley-Usmar V, Davies KJ, Dennery PA, Forman HJ, Grisham MB, Mann GE, Moore K, Roberts LJ 2nd, Ischiropoulos H. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations.. Free Radic Biol Med 2012 Jan 1;52(1):1-6.
- Wood LG, Gibson PG, Garg ML. A review of the methodology for assessing in vivo antioxidant capacity.. J Sci Food Agric 2006;86:2057–2066.
- Pleasant RS, Suagee JK, Thatcher CD, Elvinger F, Geor RJ. Adiposity, plasma insulin, leptin, lipids, and oxidative stress in mature light breed horses.. J Vet Intern Med 2013 May-Jun;27(3):576-82.
- 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.
- Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares.. Equine Vet J 1983 Oct;15(4):371-2.
- Firshman AM, Valberg SJ, Bender JB, Annandale EJ, Hayden DW. Comparison of histopathologic criteria and skeletal muscle fixation techniques for the diagnosis of polysaccharide storage myopathy in horses.. Vet Pathol 2006 May;43(3):257-69.
- Freestone JF, Wolfsheimer KJ, Kamerling SG, Church G, Hamra J, Bagwell C. Exercise induced hormonal and metabolic changes in Thoroughbred horses: effects of conditioning and acepromazine.. Equine Vet J 1991 May;23(3):219-23.
- Perkins GA, Lamb S, Erb HN, Schanbacher B, Nydam DV, Divers TJ. Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushing's disease with cyproheptadine or pergolide.. Equine Vet J 2002 Nov;34(7):679-85.
- Alves RM, Vitorino R, Figueiredo P, Duarte JA, Ferreira R, Amado F. Lifelong physical activity modulation of the skeletal muscle mitochondrial proteome in mice.. J Gerontol A Biol Sci Med Sci 2010 Aug;65(8):832-42.
- 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.
- McFarlane D, Cribb AE. Systemic and pituitary pars intermedia antioxidant capacity associated with pars intermedia oxidative stress and dysfunction in horses.. Am J Vet Res 2005 Dec;66(12):2065-72.
- Keaney JF Jr, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, Massaro JM, Sutherland P, Vita JA, Benjamin EJ. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study.. Arterioscler Thromb Vasc Biol 2003 Mar 1;23(3):434-9.
- Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, Brand MD, Cortright RN, O'Rahilly S, Montague C, Vidal-Puig AJ. Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo.. Biochem J 2003 Jul 1;373(Pt 1):155-65.
- Irrcher I, Ljubicic V, Hood DA. Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells.. Am J Physiol Cell Physiol 2009 Jan;296(1):C116-23.
- Holloway GP, Thrush AB, Heigenhauser GJ, Tandon NN, Dyck DJ, Bonen A, Spriet LL. Skeletal muscle mitochondrial FAT/CD36 content and palmitate oxidation are not decreased in obese women.. Am J Physiol Endocrinol Metab 2007 Jun;292(6):E1782-9.
- Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome.. J Clin Invest 2004 Dec;114(12):1752-61.
- Bonnard C, Durand A, Peyrol S, Chanseaume E, Chauvin MA, Morio B, Vidal H, Rieusset J. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice.. J Clin Invest 2008 Feb;118(2):789-800.
- Boden MJ, Brandon AE, Tid-Ang JD, Preston E, Wilks D, Stuart E, Cleasby ME, Turner N, Cooney GJ, Kraegen EW. Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle.. Am J Physiol Endocrinol Metab 2012 Sep 15;303(6):E798-805.
- Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.. Proc Natl Acad Sci U S A 2006 Feb 21;103(8):2653-8.
- Waller AP, Burns TA, Mudge MC, Belknap JK, Lacombe VA. Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle.. J Vet Intern Med 2011 Mar-Apr;25(2):315-21.
- Iwakami S, Misu H, Takeda T, Sugimori M, Matsugo S, Kaneko S, Takamura T. Concentration-dependent dual effects of hydrogen peroxide on insulin signal transduction in H4IIEC hepatocytes.. PLoS One 2011;6(11):e27401.
- Banse HE, McFarlane D. Comparison of three methods for evaluation of equine insulin regulation in horses of varied body condition score.. J Equine Vet Sci 2014;34:742–748.
- Bruynsteen L, Janssens GP, Harris PA, Duchateau L, Valle E, Odetti P, Vandevelde K, Buyse J, Hesta M. Changes in oxidative stress in response to different levels of energy restriction in obese ponies.. Br J Nutr 2014 Oct 28;112(8):1402-11.
- Wray H, Elliott J, Bailey SR, Harris PA, Menzies-Gow NJ. Plasma concentrations of inflammatory markers in previously laminitic ponies.. Equine Vet J 2013 Sep;45(5):546-51.
- Donaldson MT, McDonnell SM, Schanbacher BJ, Lamb SV, McFarlane D, Beech J. Variation in plasma adrenocorticotropic hormone concentration and dexamethasone suppression test results with season, age, and sex in healthy ponies and horses.. J Vet Intern Med 2005 Mar-Apr;19(2):217-22.
- Bailey SR, Habershon-Butcher JL, Ransom KJ, Elliott J, Menzies-Gow NJ. Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis.. Am J Vet Res 2008 Jan;69(1):122-9.
- Frank N, Elliott SB, Chameroy KA, Tóth F, Chumbler NS, McClamroch R. Association of season and pasture grazing with blood hormone and metabolite concentrations in horses with presumed pituitary pars intermedia dysfunction.. J Vet Intern Med 2010 Sep-Oct;24(5):1167-75.
- Borer KE, Bailey SR, Menzies-Gow NJ, Harris PA, Elliott J. Effect of feeding glucose, fructose, and inulin on blood glucose and insulin concentrations in normal ponies and those predisposed to laminitis.. J Anim Sci 2012 Sep;90(9):3003-11.
Citations
This article has been cited 5 times.- Delarocque J, Frers F, Huber K, Jung K, Feige K, Warnken T. Metabolic impact of weight variations in Icelandic horses.. PeerJ 2021;9:e10764.
- Delarocque J, Frers F, Feige K, Huber K, Jung K, Warnken T. Metabolic changes induced by oral glucose tests in horses and their diagnostic use.. J Vet Intern Med 2021 Jan;35(1):597-605.
- Kenéz Á, Warnken T, Feige K, Huber K. Lower plasma trans-4-hydroxyproline and methionine sulfoxide levels are associated with insulin dysregulation in horses.. BMC Vet Res 2018 May 2;14(1):146.
- Wang M, Yang G, Jiang X, Lu D, Mei H, Chen B. Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α (PGC-1α) Regulates the Expression of B-Cell Lymphoma/Leukemia-2 (Bcl-2) and Promotes the Survival of Mesenchymal Stem Cells (MSCs) via PGC-1α/ERRα Interaction in the Absence of Serum, Hypoxia, and High Glucose Conditions.. Med Sci Monit 2017 Jul 16;23:3451-3460.
- Collins KH, Hart DA, Smith IC, Issler AM, Reimer RA, Seerattan RA, Rios JL, Herzog W. Acute and chronic changes in rat soleus muscle after high-fat high-sucrose diet.. Physiol Rep 2017 May;5(10):e13270.