Fatness, fitness and affliction: are there inflammatory consequences to exercise when you're a fat pony?

超过三分之一的国内马匹超重，肥胖是发展炎症性疾病(如骨关节炎)的重要风险因素，无论是直接通过局部产生炎性化合物和/或间接通过胃肠道屏障的破坏和有毒化合物的渗漏进入血液循环。运动通常出现在马匹减肥的第一线，但我们之前的研究表明，高强度运动的马匹血液和滑液中的炎症介质浓度会升高。我们迫切需要关于运动对超重动物有益和有害影响之间微妙平衡的信息，以便为不会进一步破坏关节内环境平衡的适当运动养生法提供建议。我们已经成功地利用软骨外植体在炎症刺激下与自体脂肪组织共培养建立了脂肪中心性软骨炎症的体外模型，这些研究清楚地证明了在炎症事件中脂肪组织具有显著的细胞毒性作用，并提出了关于超重动物软骨对运动炎症效应的反应的重要问题。这项研究的目的是描述运动和抗炎药物对超重小马炎症的急性和长期影响。实验将包括比较代谢健康、超重(MHO)和健康体重(HW)小马与未锻炼的MHO和HW小马对运动的炎症反应和恢复情况。在完成运动测试前48小时以及完成运动测试后1、8和12小时采集的血液(BL)和滑液(SF)样本将被分析，以确定在炎症、炎症消退、软骨破坏和胃肠道屏障功能(即肠漏)破坏期间增加的化合物。休息4周后，每个重量类别的锻炼组和非锻炼组将互换，重复试验，然后小马将开始为期60天的训练方案。训练结束后，每个体重类别的一半小马将在最后一次运动测试之前每天接受一次口服非甾体抗炎药，为期5天(每个体重类别的其余小马不接受非甾体抗炎药)。结果测量将包括上述措施，并增加每周身体成分测量，包括体脂(臀部脂肪超声)、体重(称重器)和周长(软带)。这项研究将首次描述在存在和不存在非类固醇抗炎药的情况下，运动对超重小马的BL和SF的炎症效应，确定运动对MHO小马的生理益处和/或风险。了解运动和肥胖的联合炎症特征将预防运动导致的肥胖相关炎症性疾病，如骨性关节炎。

More than a third of domestic equids are overweight, and obesity is an important risk factor for development of inflammatory diseases such as osteoarthritis (OA), either directly via local production of inflammatory compounds and/or indirectly via a breakdown in the gastrointestinal barrier and leakage of toxic compounds into the circulation. Exercise often emerges on the front line of equine weight loss, but our previous studies have shown that horses exercising at high intensity have elevated concentrations of inflammatory mediators in blood and synovial fluid. Information on the delicate balance between beneficial and detrimental effects of exercise in overweight animals is desperately needed in order to advise appropriate exercise regimens that will not further compromise joint homeostasis. We have successfully developed in vitro models of adipocentric cartilage inflammation using cartilage explants co-cultured with autologous adipose tissue in the presence of an inflammatory stimulus, and these studies clearly demonstrate a marked cytotoxic effect of adipose tissue during an inflammatory event, and raise important questions about the response of cartilage to the inflammatory effects of exercise in overweight animals. The objectives of this study are to characterize acute and long-term effects of exercise and anti-inflammatory drugs on inflammation in overweight ponies. Experiments will include comparisons of inflammatory response to and recovery from exercise in metabolically healthy, overweight (MHO) and healthy weight (HW) ponies, compared with unexercised MHO and HW ponies. Blood (BL) and synovial fluid (SF) samples obtained 48 h prior to and 1, 8 and 12 h after completion of an exercise test will be analyzed for compounds which are increased during inflammation, inflammation resolution, cartilage breakdown, and breakdown of gastrointestinal barrier function (ie leaky gut'). After a 4-week break, exercised and non-exercised groups within each weight category will be crossed over and the trial will be repeated, and then ponies will embark upon a 60-day training regimen. Immediately following completion of training, half the ponies from each weight category will receive an oral dose of NSAID daily for 5 days (remaining ponies in each weight category receive no NSAID) prior to a final exercise test. Outcome measures will include those described above, with the addition of weekly measures of body composition measurements, including body fat (rump-fat ultrasound), body weight (weighbridge) and girth circumference (flexible tape). This research will be the first to characterize inflammatory effects of exercise in BL and SF in overweight ponies, in the presence and absence of NSAIDs, identifying physiological benefits and/or risks of exercise in MHO ponies. An understanding of the combined inflammatory profile of exercise and obesity will pre-empt exercise-induced promotion of obesity-associated inflammatory disorders such as OA.