title: 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.
authors.affiliation: 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).
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Banse
authors.affiliation: 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).
authors.forename: Nicholas
authors.initials: N
authors.lastname: Frank
authors.affiliation: 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).
authors.forename: Grace P S
authors.initials: GP
authors.lastname: Kwong
authors.affiliation: 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).
authors.forename: Dianne
authors.initials: D
authors.lastname: McFarlane
mesh_terms: D000818:Animals; D015415:Biomarkers; D001823:Body Composition; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D006946:Hyperinsulinism / Q000209:etiology / Q000662:veterinary*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000662:veterinary*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D015415:Biomarkers