A K Hahn1, A Batushansky2, R A Rawle3, E B Prado Lopes2, R K June4, T M Griffin5. 1. Molecular Biosciences Program, Montana State University, Bozeman, MT, 59717, USA; Department of Cell Biology & Neuroscience, Montana State University, Bozeman, MT, 59717, USA; Department of Biological and Environmental Sciences, Carroll College, Helena, MT, 59625, USA. 2. Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, 73104, USA. 3. Molecular Biosciences Program, Montana State University, Bozeman, MT, 59717, USA; Department of Microbiology & Immunology, Montana State University, Bozeman, MT, 59717, USA. 4. Molecular Biosciences Program, Montana State University, Bozeman, MT, 59717, USA; Department of Cell Biology & Neuroscience, Montana State University, Bozeman, MT, 59717, USA; Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, USA. Electronic address: rjune@montana.edu. 5. Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, 73104, USA; Reynolds Oklahoma Center on Aging, Department of Biochemistry and Molecular Biology, Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA. Electronic address: Tim-Griffin@omrf.org.
Abstract
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. Published by Elsevier Ltd.
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. Published by Elsevier Ltd.
Entities:
Keywords:
Exercise; Metabolomics; Obesity; Osteoarthritis; Synovial fluid; Systems biology
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