{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:13:08Z","timestamp":1791227588049,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T00:00:00Z","timestamp":1647043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000964","name":"Arthritis National Research Foundation","doi-asserted-by":"publisher","award":["833836"],"award-info":[{"award-number":["833836"]}],"id":[{"id":"10.13039\/100000964","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010874","name":"American Society for Bone and Mineral Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010874","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Obesity promotes the development of osteoarthritis (OA). It is also well\u2010established that obesity leads to excessive lipid deposition in nonadipose tissues, which often induces lipotoxicity. The objective of this study was to investigate changes in the levels of various lipids in mouse cartilage in the context of obesity and determine if chondrocyte de novo lipogenesis is altered.\u00a0We used Oil Red O to determine the accumulation of lipid droplets in cartilage from mice fed high\u2010fat diet (HFD) or low\u2010fat diet (LFD). We further used mass spectrometry\u2010based lipidomic analyses to quantify levels of different lipid species. Expression of genes involving in fatty acid (FA) uptake, synthesis, elongation, and desaturation were examined using quantitative polymerase chain reaction. To further study the potential mechanisms, we cultured primary mouse chondrocytes under high\u2010glucose and high\u2010insulin conditions to mimic the local microenvironment associated with obesity and subsequently examined the abundance of cellular lipid droplets. The acetyl\u2010CoA carboxylase (ACC) inhibitor, ND\u2010630, was added to the culture medium to examine the effect of inhibiting de novo lipogenesis on lipid accumulation in chondrocytes.\u00a0When compared to the mice receiving LFD, the HFD group displayed more chondrocytes with visible intracellular lipid droplets. Significantly higher amounts of total FAs were also detected in the HFD group. Five out of six significantly upregulated FAs were \u03c9\u20106 FAs, while the two significantly downregulated FAs were \u03c9\u20103 FAs. Consequently, the HFD group displayed a significantly higher \u03c9\u20106\/\u03c9\u20103 FA ratio. Ether linked phosphatidylcholine was also found to be higher in the HFD group. Fatty acid desaturase (<jats:italic>Fad1\u20103<\/jats:italic>), fatty acid\u2010binding protein 4 <jats:italic>(Fabp4<\/jats:italic>), and fatty acid synthase (<jats:italic>Fasn<\/jats:italic>) transcripts were not found to be different between the treatment groups and fatty acid elongase (<jats:italic>Elovl1\u20107<\/jats:italic>) transcripts were undetectable in cartilage. Ceramide synthase 2 (<jats:italic>Cers\u20102<\/jats:italic>), the only transcript found to be changed in these studies, was significantly upregulated in the HFD group. In vitro, chondrocytes upregulated de novo lipogenesis when cultured under high\u2010glucose, high\u2010insulin conditions, and this observation was associated with the activation of ACC, which was attenuated by the addition of ND\u2010630.\u00a0This study provides the first evidence that lipid deposition is increased in cartilage with obesity and that this is associated with the upregulation of ACC\u2010mediated de novo lipogenesis. This was supported by our observation that ACC inhibition ameliorated lipid accumulation in chondrocytes, thereby suggesting that ACC could potentially be targeted to treat obesity\u2010associated OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jor.25322","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T03:13:15Z","timestamp":1647141195000},"page":"2771-2779","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Obesity promotes lipid accumulation in mouse cartilage\u2014A potential role of acetyl\u2010CoA carboxylase (ACC) mediated chondrocyte de novo lipogenesis"],"prefix":"10.1002","volume":"40","author":[{"given":"Huanhuan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Ohio University Athens Ohio USA"},{"name":"Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Witzigreuter","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Ohio University Athens Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshini","family":"Sathiaseelan","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin\u2010Paul","family":"Agbaga","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA"},{"name":"Dean A. McGee Eye Institute Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Brush","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA"},{"name":"Dean A. McGee Eye Institute Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Stout","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-1504","authenticated-orcid":false,"given":"Shouan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Ohio University Athens Ohio USA"},{"name":"Ohio Musculoskeletal and Neurological Institute (OMNI) Ohio University Athens Ohio 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