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

超过三分之一的家畜超重，肥胖是骨关节炎（OA）等炎症性疾病发展的重要危险因素，要么直接通过局部产生炎症性化合物，要么间接通过胃肠道屏障的破坏和有毒化合物泄漏到循环系统中。运动经常出现在马减肥的第一线，但我们之前的研究表明，高强度运动的马血液和滑液中炎症介质的浓度升高。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，以便建议适当的运动方案，而不会进一步损害关节内稳态。我们已经成功地在体外建立了脂肪中心软骨炎症模型，使用软骨外植体与自体脂肪组织在炎症刺激下共同培养，这些研究清楚地表明，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。本研究的目的是表征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）的小马与未运动的MHO和HW小马对运动的炎症反应和恢复情况。在运动测试完成前48小时和完成后1、8和12小时采集血液（BL）和滑液（SF）样本，分析炎症、炎症消退、软骨破坏和胃肠道屏障功能破坏（即“漏肠”）期间增加的化合物。休息4周后，每个体重类别的运动组和非运动组将被交叉，重复试验，然后小马将开始为期60天的训练计划。训练完成后，在最后的运动测试之前，每个体重类别的一半小马将每天口服NSAID 5天（每个体重类别的其余小马不服用NSAID）。结果测量将包括上述内容，加上每周测量身体成分，包括体脂（臀脂超声）、体重（体重桥）和周长（软性带）。这项研究将首次描述运动对超重小马的BL和SF的炎症作用，在有无非甾体抗炎药的情况下，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诱导的肥胖相关炎症疾病（如OA）的促进。

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.