Banse Heidi E, Frank Nicholas, Kwong Grace P S, 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).
Can J Vet Res. 2015 Oct;79(4):329-38.
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.
在马中，高胰岛素血症和胰岛素抵抗（胰岛素调节异常）与蹄叶炎的发生有关。虽然肥胖与胰岛素调节异常有关，但肥胖相关的胰岛素调节异常机制仍有待确定。我们假设骨骼肌中的氧化应激与马的肥胖相关高胰岛素血症有关。对35匹体况评分（BCS）为3/9至9/9的轻型马进行了研究，其中包括7匹肥胖、正常胰岛素水平（BCS≥7，静息血清胰岛素<30μIU/mL）的马和6匹肥胖、高胰岛素水平（静息血清胰岛素≥30μIU/mL）的马。在骨骼肌活检中评估氧化应激标志物（氧化损伤、线粒体功能和抗氧化能力）。使用Spearman等级相关系数来确定氧化应激标志物与BCS之间的关系。此外，为了评估氧化应激在肥胖相关高胰岛素血症中的作用，比较了瘦、正常胰岛素水平（L-NI）；肥胖、正常胰岛素水平（O-NI）；以及肥胖、高胰岛素水平（O-HI）马之间的抗氧化能力和氧化损伤标志物。BCS的增加与负责线粒体生物发生的线粒体蛋白（雌激素相关受体α，ERRα）的基因表达增加以及抗氧化酶总超氧化物歧化酶（TotSOD）活性增加有关。当比较各组（L-NI、O-NI和O-HI）时，与L-NI马相比，O-HI马的TotSOD活性增加，氧化损伤标志物蛋白质羰基减少。这些发现表明肥胖动物的肌肉中发生了保护性抗氧化反应，并且骨骼肌中与肥胖相关的氧化损伤不是马高胰岛素血症发病机制的核心。
