{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:38:44Z","timestamp":1792679924924,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T00:00:00Z","timestamp":1327622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To test the hypotheses that obesity due to a very high\u2010fat diet induces knee osteoarthritis (OA), and that short\u2010term wheel\u2010running exercise protects against obesity\u2010induced knee OA by reducing systemic inflammation and metabolic dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male C57BL\/6J mice were fed either a control diet (13.5% kcal from fat) or a very high\u2010fat diet (60% kcal from fat) from age 12 weeks to age 24 weeks. From 20 to 24 weeks of age, half of the mice were housed with running wheels. The severity of knee OA was determined by assessing histopathologic features, and serum cytokines were measured using a multiplex bead immunoassay and enzyme\u2010linked immunosorbent assays. Body composition was quantified by dual\u2010energy x\u2010ray absorptiometry, and insulin resistance was assessed by glucose tolerance testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Feeding mice with a very high\u2010fat diet increased knee OA scores and levels of serum leptin, adiponectin, KC (mouse analog of interleukin\u20108 [IL\u20108]), monokine induced by interferon\u2010\u03b3 (CXCL9), and IL\u20101 receptor antagonist to an extent in proportion to the gain in body fat (3\u2010fold increase in percent body fat compared to controls). Wheel\u2010running exercise reduced progression of OA in the medial femur of obese mice. In addition, exercise disrupted the clustering of cytokine expression and improved glucose tolerance, without reducing body fat or cytokine levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Obesity induced by a very high\u2010fat diet in mice causes OA and systemic inflammation in proportion to body fat. Increased joint loading is not sufficient to explain the increased incidence of knee OA with obesity, as wheel running is protective rather than damaging. Exercise improves glucose tolerance and disrupts the coexpression of proinflammatory cytokines, suggesting that increased aerobic exercise may act independently of weight loss in promoting joint health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.33332","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T22:33:54Z","timestamp":1317162834000},"page":"443-453","source":"Crossref","is-referenced-by-count":218,"title":["Induction of osteoarthritis and metabolic inflammation by a very high\u2010fat diet in mice: Effects of short\u2010term exercise"],"prefix":"10.1002","volume":"64","author":[{"given":"Timothy M.","family":"Griffin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet L.","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia 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