Effects of long-term exercise and a high-fat diet on synovial fluid metabolomics and joint structural phenotypes in mice: an integrated network analysis. Issue 11 (November 2021)

• Record Type: Journal Article
• Authors: Hahn, A.K.; Batushansky, A.; Rawle, R.A.; Prado Lopes, E.B.; June, R.K.; Griffin, T.M.
• Is Part Of: Osteoarthritis and cartilage. Volume 29:Issue 11(2021)
• Page Start: 1549
• Page End: 1563
• Publication Date: 2021-11
• Subjects: Osteoarthritis -- Obesity -- Exercise -- Metabolomics -- Synovial fluid -- Systems biology; OA osteoarthritis -- HF high-fat -- CF control-fat -- SF synovial fluid -- Ex exercise -- Sed sedentary -- GTT glucose tolerance test -- AUC area under the curve -- LC-MS liquid chromatography-mass spectrometry -- m/z mass-to-charge ratio -- HCA hierarchical cluster analysis; Osteoarthritis -- Periodicals; Cartilage -- Periodicals; Osteoarthritis -- Periodicals; Cartilage -- Periodicals; Arthrose -- Périodiques; Articulations -- Maladies -- Périodiques; 616.7223005
• DOI: 10.1016/j.joca.2021.08.008
• Languages: English
• ISSNs: 1063-4584

Abstract

Summary: Objective: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. Methods: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age ( n = 9–13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. Results: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1, 412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1β and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. Conclusion: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.