DOES INHERENT AEROBIC CAPACITY PROTECT THE KNEE JOINT FROM DEGENERATION IN A DIET-INDUCED PRE-CLINICAL MODEL OF OBESITY?

Introduction: Obesity and associated metabolic syndrome are risk factors in the development of knee joint osteoarthritis and other musculoskeletal degeneration in humans and pre-clinical animal models such as rats1. In obese animals, muscle fibrosis and fat infiltration were observed primarily in Type II muscle fibers, which have limited aerobic capacity. Furthermore, previous studies have shown that aerobic training in Sprague Dawley rats had a protective effect in knee joint integrity in rats exposed to a high fat/high sucrose (HFHS) diet compared to rats exposed to the HFHS diet but not undergoing aerobic activity3. Based on this evidence that aerobic capacity may play a role in metabolic and musculoskeletal disease, we used an animal model of selective breeding for high and low aerobic capacity, hereafter referred to as high-capacity runners (HCR) and low-capacity runners (LCR). Studies have demonstrated that HCR rats have lower weight gain when exposed to a high fat and/or sugar diets, less metabolic complications, a reduced insulin resistance, less diabetes, and a decreased risk of cardiovascular disease when compared to the LCR rats4. The aim of this study was to test if inherent aerobic capacity protects the knee joint from degeneration in an established pre-clinical rat model of diet-induced obesity and metabolic syndrome.

Materials and

Methods: Thirty-six twenty-four week-old male N:NIH rats (LCR; n=18, and HCR; n= 18) were split evenly and randomized to either a HFHS diet or a chow diet for 12 weeks. During the intervention period, the animals were scanned at baseline, midpoint and endpoint using a dual-energy X-ray absorptiometry. After the intervention period, knee joints were harvested, fixed in formalin, decalcified in Cal X II and processed in paraffin wax. Serial sagittal sections were cut at 10um and stained sequentially in Gills 2 Hematoxylin, Fast green and Safranin O. Sections were evaluated by two independent blinded scorers and scores were determined using a modified Mankin OA scoring system.

Results, Conclusions, and Discussions: Both groups subjected to the HFHS diet experienced an increase in body fat content compared to their counterparts fed the standard chow diet. LCR and HCR animals fed the HFHS diet showed mean body fat percentages of 44 ± 5% and 41 ± 6%, respectively, in contrast to their chow-fed counterparts, which exhibited mean body fat percentages of 30 ± 5.5% and 29 ± 4%, respectively. The LCR animals exhibited slightly higher mean body fat percentages compared to HCR animals when subjected to the HFHS diet, suggesting the existence of potential group-specific variations in metabolic responses to dietary alterations, however the difference was not statistically significant. After the 12 weeks of diet intervention, the LCR group animals had significantly increased Modified-Mankin scores compared to the HCR group animals, regardless of the diet (p < 0.05). This result suggests that inherent high aerobic capacity, represented by the HCR strain, may have a protective effect against metabolically induced degeneration of the knee joint. This is an interesting observation that underscores the potential interplay between metabolic health and joint integrity. There was no significant difference observed in Modified-Mankin scores between the two diets within each strain, however a trend was apparent in the LCR group, here the HFHS diet resulted in increased Modified-Mankin scores, when compared to the chow-fed group. This finding suggests that while diet composition may influence body fat content, it may not have a significant direct impact on joint health, at least within the context of this study and the parameters measured.
The unique metabolic profiles in the LCR and HCR strains might point to crucial metabolic factors responsible for the metabolically induced degeneration of the musculoskeletal system. Furthermore, this pre-clinical research might inform clinical trials using patients with obesity and at risk of knee joint osteoarthritis by providing mechanistic insights into pathways in obesity that lead to joint degeneration, as well as insight into treatment modalities through aerobic capacity training.

Acknowledgements (Optional): CIHR, McCaig Institute for Bone and Joint Health, the Nigg Chair for Biomechanics, and the Killam Foundation.