Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice
Abstract We hypothesized that daily exercise promotes joint health by upregulating anti-inflammatory mediators via adaptive molecular and metabolic changes in the infrapatellar fat pad (IFP). We tested this hypothesis by conducting time-resolved analyses between 1 and 14 days of voluntary wheel runn...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86726-0 |
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| author | Timothy M. Griffin Ravi K. Komaravolu Erika Barboza Prado Lopes Padmaja Mehta-D’souza Taylor Conner Tessa Kovats Susan Kovats Madeline Allen Peyton Harris Mary Beth Humphrey Hope D. Welhaven Priyanka Brahmachary Ronald K. June |
| author_facet | Timothy M. Griffin Ravi K. Komaravolu Erika Barboza Prado Lopes Padmaja Mehta-D’souza Taylor Conner Tessa Kovats Susan Kovats Madeline Allen Peyton Harris Mary Beth Humphrey Hope D. Welhaven Priyanka Brahmachary Ronald K. June |
| author_sort | Timothy M. Griffin |
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| description | Abstract We hypothesized that daily exercise promotes joint health by upregulating anti-inflammatory mediators via adaptive molecular and metabolic changes in the infrapatellar fat pad (IFP). We tested this hypothesis by conducting time-resolved analyses between 1 and 14 days of voluntary wheel running exercise in C57BL/6J mice. IFP structure and cellularity were evaluated by histomorphology, picrosirius red collagen staining, and flow cytometry analysis of stromal vascular fraction cells. Joint inflammation and metabolism were evaluated by multiplex gene expression analysis of synovium-IFP tissue and synovial fluid metabolomics, respectively. Exercise transiently increased cytokine and chemokine gene expression in synovium-IFP tissue, resolving within the first 5 days of exercise. The acute inflammatory response was associated with decreased adipocyte size and elevated CD45+Gr1+ myeloid cells, increased collagen content, and oxidized phospholipids. Exercise acutely altered synovial fluid metabolites, characterized by increased amino acids, peptides, bile acids, sphingolipids, dicarboxylic acids, and straight medium chain fatty acids and decreased hydroxy fatty acids and diacylglycerols. Between 5 and 14 days of exercise, inflammation, collagen, and adipocyte size returned to pre-exercise levels, and CD206+ immuno-regulatory macrophages increased. Thus, although the onset of new daily exercise transiently induced synovium-IFP inflammation and altered tissue structure, sustained daily exercise promoted IFP homeostasis. |
| format | Article |
| id | doaj-art-0a562a47bfdb4701b84dac351e23a911 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0a562a47bfdb4701b84dac351e23a9112025-01-19T12:23:41ZengNature PortfolioScientific Reports2045-23222025-01-0115111810.1038/s41598-025-86726-0Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in miceTimothy M. Griffin0Ravi K. Komaravolu1Erika Barboza Prado Lopes2Padmaja Mehta-D’souza3Taylor Conner4Tessa Kovats5Susan Kovats6Madeline Allen7Peyton Harris8Mary Beth Humphrey9Hope D. Welhaven10Priyanka Brahmachary11Ronald K. June12Aging and Metabolism Research Program, Oklahoma Medical Research FoundationAging and Metabolism Research Program, Oklahoma Medical Research FoundationAging and Metabolism Research Program, Oklahoma Medical Research FoundationAging and Metabolism Research Program, Oklahoma Medical Research FoundationAging and Metabolism Research Program, Oklahoma Medical Research FoundationAging and Metabolism Research Program, Oklahoma Medical Research FoundationArthritis and Clinical Immunology Research Program, Oklahoma Medical Research FoundationDepartment of Health and Exercise Science, University of OklahomaDepartment of Biology, University of OklahomaVeterans Affairs Medical CenterDepartment of Chemistry & Biochemistry, Montana State UniversityDepartment of Mechanical & Industrial Engineering, Montana State UniversityDepartment of Mechanical & Industrial Engineering, Montana State UniversityAbstract We hypothesized that daily exercise promotes joint health by upregulating anti-inflammatory mediators via adaptive molecular and metabolic changes in the infrapatellar fat pad (IFP). We tested this hypothesis by conducting time-resolved analyses between 1 and 14 days of voluntary wheel running exercise in C57BL/6J mice. IFP structure and cellularity were evaluated by histomorphology, picrosirius red collagen staining, and flow cytometry analysis of stromal vascular fraction cells. Joint inflammation and metabolism were evaluated by multiplex gene expression analysis of synovium-IFP tissue and synovial fluid metabolomics, respectively. Exercise transiently increased cytokine and chemokine gene expression in synovium-IFP tissue, resolving within the first 5 days of exercise. The acute inflammatory response was associated with decreased adipocyte size and elevated CD45+Gr1+ myeloid cells, increased collagen content, and oxidized phospholipids. Exercise acutely altered synovial fluid metabolites, characterized by increased amino acids, peptides, bile acids, sphingolipids, dicarboxylic acids, and straight medium chain fatty acids and decreased hydroxy fatty acids and diacylglycerols. Between 5 and 14 days of exercise, inflammation, collagen, and adipocyte size returned to pre-exercise levels, and CD206+ immuno-regulatory macrophages increased. Thus, although the onset of new daily exercise transiently induced synovium-IFP inflammation and altered tissue structure, sustained daily exercise promoted IFP homeostasis.https://doi.org/10.1038/s41598-025-86726-0Hoffa’s fat padAdipocyteSynoviumMetabolomicsMetaflammationRunning |
| spellingShingle | Timothy M. Griffin Ravi K. Komaravolu Erika Barboza Prado Lopes Padmaja Mehta-D’souza Taylor Conner Tessa Kovats Susan Kovats Madeline Allen Peyton Harris Mary Beth Humphrey Hope D. Welhaven Priyanka Brahmachary Ronald K. June Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice Scientific Reports Hoffa’s fat pad Adipocyte Synovium Metabolomics Metaflammation Running |
| title | Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice |
| title_full | Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice |
| title_fullStr | Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice |
| title_full_unstemmed | Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice |
| title_short | Exercise induces dynamic changes in intra-articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice |
| title_sort | exercise induces dynamic changes in intra articular metabolism and inflammation associated with remodeling of the infrapatellar fat pad in mice |
| topic | Hoffa’s fat pad Adipocyte Synovium Metabolomics Metaflammation Running |
| url | https://doi.org/10.1038/s41598-025-86726-0 |
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