Abstract
BACKGROUND: The Intensive Diet and Exercise for Arthritis (IDEA) trial was a randomized trial conducted to evaluate the effects of diet and exercise on osteoarthritis (OA), the most prevalent form of arthritis. Various risk factors, including obesity and sex, contribute to OA's debilitating nature. While diet and exercise are known to improve OA symptoms, cellular and molecular mechanisms underlying these interventions, as well as effects of participant sex, remain elusive. METHODS: Serum was obtained at three timepoints from IDEA participants assigned to groups of diet, exercise, or combined diet and exercise (n = 10 per group). A randomly selected subset of serum samples were extracted and analyzed via liquid chromatography-mass spectrometry combined with metabolomic profiling to unveil mechanisms associated with types of intervention and disease. Extracted serum was pooled and fragmentation patterns were analyzed to identify metabolites that statistically differentially regulated between groups. RESULTS: Changes in metabolism across male and female IDEA participants after 18-months of diet, exercise, and combined diet and exercise intervention mapped to lipid, amino acid, carbohydrate, vitamin, and matrix metabolism. The diverse metabolic landscape detected across IDEA participants shows that intervention type differentially impacts the serum metabolome of OA individuals. Moreover, dissimilarities in the serum metabolome corresponded with participant sex. CONCLUSIONS: These findings suggest that intensive weight loss among males and females offers potential metabolic benefits for individuals with knee OA. This study provides a deeper understanding of dysregulation occurring during OA development in parallel with various interventions, potentially paving the way for improved interventions, treatments, and quality of life of those impacted by OA. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00381290, Registered, 9/25/2006.