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Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2015; 79(4); 329-338;

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.

Abstract: In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia. Chez les chevaux l’hyperinsulinémie et la résistance à l’insuline (dérèglement de l’insuline) sont associées avec le développement de fourbure. Bien que l’obésité soit associée avec le dérèglement de l’insuline, le mécanisme de l’obésité associée au dérèglement de l’insuline demeure à être établi. Nous émettons l’hypothèse que le stress oxydatif dans les muscles squelettiques est associé avec l’obésité associée à l’hyperinsulinémie chez les chevaux. Trente-cinq chevaux de races légères avec des pointages de conditions corporelles (PCC) de 3/9 à 9/9 ont été étudiés, incluant sept chevaux obèses, normo-insulinémique (PCC ≥ 7, insuline sérique au repos < 30 μIU/mL) et six chevaux obèses, hyperinsulinémique (insuline sérique au repos ≥ 30 μIU/mL). Les marqueurs de stress oxydatif (damage oxydatif, fonction mitochondriale, et capacité antioxydante) furent évalués dans des biopsies de muscles squelettiques. Un coefficient de corrélation de rang de Spearman a été utilisé pour déterminer la relation entre les marqueurs de stress oxydatif et le PCC. De plus, pour évaluer le rôle du stress oxydatif dans l’obésité reliée à l’hyperinsulinémie, les marqueurs de la capacité anti-oxydante et des dommages oxydatifs ont été comparés entre des chevaux minces, normo-insulinémiques (L-NI); des chevaux obèses, normo-insulinémique (O-NI); et des chevaux obèses, hyperinsulinémiques (O-HI). Une augmentation des PCCs était associée avec une augmentation de l’expression des gènes d’une protéine mitochondriale responsable de la biogénèse des mitochondries (récepteur alpha apparenté aux estrogènes, ERRα) et d’une augmentation de l’activité anti-oxydante totale de l’enzyme superoxyde dismutase (TotSOD). Lors de la comparaison des groupes (L-NI, O-NI, et O-HI), l’activité TotSOD était augmentée et les carbonyles protéiques, un marqueur des dommages oxydatifs, avaient diminué chez les chevaux O-HI comparativement aux chevaux L-NI. Ces données suggèrent qu’une réponse anti-oxydante protectrice s’est produite dans le muscle des chevaux obèses et que le dommage oxydatif associés à l’obésité dans les muscles squelettiques n’est pas central à la pathogénèse de l’hyperinsulinémie équine.(Traduit par Docteur Serge Messier).
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Publication Date: 2015-10-02 PubMed ID: 26424915PubMed Central: PMC4581679
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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 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

APA
Banse HE, Frank N, Kwong GP, McFarlane D. (2015). Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses. Can J Vet Res, 79(4), 329-338.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 1928-9022
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 79
Issue: 4
Pages: 329-338

Researcher Affiliations

Banse, Heidi E
  • 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).
Frank, Nicholas
  • 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).
Kwong, Grace P S
  • 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).
McFarlane, Dianne
  • 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

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