{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:13:50Z","timestamp":1790363630854,"version":"4.1.0"},"reference-count":44,"publisher":"SAGE Publications","issue":"14","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Fatty infiltration of the rotator cuff muscle is a critical prognostic factor associated with poor tendon healing and high retear rates after rotator cuff tear (RCT). Recent studies have identified fatty acid binding protein 4 (FABP4) as a hypoxia- and inflammation-responsive lipid chaperone that may drive adipogenic degeneration in injured muscle tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To evaluate whether fenofibrate\u2014a peroxisome proliferator-activated receptor alpha (PPAR\u03b1) agonist approved for the treatment of hyperlipidemia\u2014could prevent fatty infiltration by modulating FABP4 expression in vitro and in a RCT repair rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Controlled laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The expression of FABP4 under hypoxic conditions was evaluated in C2C12 myoblasts treated with fenofibrate (10 and 100 \u03bcm) using quantitative real-time polymerase chain reaction (qRT-PCR). To investigate molecular mechanisms, the expression levels of upstream regulators and adipocyte differentiation\u2013related genes were also measured by qRT-PCR after fenofibrate treatment in the same cell line. For the in vivo study, an RCT model was established by transection of the right supraspinatus tendon. Fenofibrate (20 mg\/kg) was locally administered 3 times over 2 days after surgery. At 6 weeks, the supraspinatus muscle was harvested. Fatty infiltration was qualitatively and quantitatively assessed using histological analysis, and the expression of relevant metabolic and adipogenic genes was analyzed by qRT-PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In vitro, fenofibrate significantly downregulated FABP4 expression in a dose-dependent manner under hypoxic conditions (fenofibrate, 10 \u00b5m: 0.86 \u00b1 0.12 [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01]; 100 \u00b5m: 0.32 \u00b1 0.06 [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01]; control: 1.12 \u00b1 0.17). Expression of PPAR\u03b1 (fenofibrate, 10 \u00b5m: 2.46 \u00b1 0.10 [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01]; 100 \u00b5m: 2.75 \u00b1 0.13 [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01]; control: 1 \u00b1 0.10), an upstream regulator of FABP4, was significantly upregulated after treatment in a similarly dose-dependent fashion. In vivo, fenofibrate-treated shoulders demonstrated marked suppression of fatty infiltration, as confirmed by both qualitative histological evaluation and quantitative fat area analysis (fenofibrate: 6.66% \u00b1 10.38%; control: 46.38% \u00b1 21.79% [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01]). Gene expression profiling revealed that PPAR\u03b1 was significantly upregulated (fenofibrate: 10.65 \u00b1 7.02; control: 1 \u00b1 0.62 [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 005]), while FABP4 expression was significantly reduced (fenofibrate: 2.64 \u00b1 0.91; control: 5.44 \u00b1 2 [\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .05]) in the fenofibrate group compared with controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Fenofibrate reduces muscle fatty infiltration by modulating the PPAR\u03b1-FABP4 metabolic pathway in the setting of RCT. These findings support the potential of fenofibrate as a drug repositioning candidate to prevent muscle degeneration and enhance tissue quality in rotator cuff (RC) injuries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>Fenofibrate, with its established clinical safety profile, may represent a novel pharmacologic strategy to improve outcomes after RC repair by targeting fatty infiltration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03635465251382858","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T11:15:29Z","timestamp":1761131729000},"page":"3474-3482","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Fenofibrate Attenuates Rotator Cuff Muscle Fatty Infiltration via Modulation of the PPAR\u03b1-FABP4 Pathway"],"prefix":"10.1177","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6869-0788","authenticated-orcid":false,"given":"Sung-Jin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Center for Shoulder and Elbow Surgery, Konkuk University School of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6449-8341","authenticated-orcid":false,"given":"Yong-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Cartilage Regeneration, Barunsesang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6446-6254","authenticated-orcid":false,"given":"Jong Pil","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-9289","authenticated-orcid":false,"given":"Seok Won","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Center for Shoulder and Elbow Surgery, Konkuk University School of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0532"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-016-0118-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jse.2013.07.039"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-021-00265-6"},{"issue":"1","key":"e_1_3_2_7_2","first-page":"93","article-title":"The role of vitamin D in shoulder health: a comprehensive review of its impact on rotator cuff tears and surgical results","volume":"28","author":"Daher M","year":"2025","unstructured":"Daher M, Covarrubias O, Lopez R, et al. 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