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

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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.