{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:53:40Z","timestamp":1785200020410,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Excessive fat accumulation in muscles with disuse atrophy may impair muscle physiologic function and exacerbate the progression of atrophy, with causes largely unexplored. Evidence indicates leptin plays a crucial role in regulating skeletal muscle fat metabolism. Masticatory muscle (a special skeletal muscle) atrophy often causes aesthetic and functional problems due to various occlusal factors. This study examines leptin's role and mechanism in masseter muscle disuse atrophy and explores leptin's source.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A C57BL\/6J mouse disuse atrophy model was established. The ameliorative role of leptin in masseter muscle lipid accumulation and atrophy and its local sources were explored by injection of exogenous leptin and nilotinib, which specifically induces leptin\u2010producing fibro\u2010adipogenic progenitor cells (FAPs). Transcriptomic sequencing revealed the molecular mechanism of lipid accumulation in the masseter muscle, which was validated by in\u00a0vitro experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mice with masseter muscle disuse atrophy showed significant fat accumulation (triglycerides, TG: 3.750\u2010fold elevation,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Local leptin injection reduced masseter muscle fat accumulation (TG: 2.330\u2010fold reduction,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and atrophy index (MuRF\u20101: 2.068\u2010fold reduction,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Transcriptomic analysis revealed downregulated PPAR lipid metabolism pathways, with significant repression of peroxisome proliferator\u2010activated receptor \u03b1 (PPAR\u03b1) and consequent phenotypic effects. Leptin significantly upregulated PPAR\u03b1 expression (mRNA: 10.814\u2010fold elevation,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; protein: 1.843\u2010fold elevation,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). PPAR\u03b1 silencing in C2C12 cells abrogated leptin's lipid\u2010lowering effect (TG: 3.903\u2010fold reduction abolished,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Fluorescence\u2010activated cell sorting (FACS)\u2010isolated FAPs expressed leptin mRNA. Nilotinib\u2010induced FAP apoptosis reduced local leptin expression (1.628\u2010fold reduction,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and exacerbated masseter muscle lipid accumulation and atrophy (MuRF\u20101: 2.007\u2010fold elevation,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Disuse atrophy reduces leptin secreted by FAPs, triggering lipid accumulation that exacerbates muscle degeneration. This reveals the critical regulatory role of FAPs in maintaining masseter muscle homeostasis through leptin\u2010mediated mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70141","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T06:49:37Z","timestamp":1764226177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Leptin From Fibro\u2010Adipogenic Progenitor Cells (FAPs) Regulates Masseter Muscle Disuse Atrophy and Ectopic Fat Accumulation"],"prefix":"10.1002","volume":"16","author":[{"given":"Song","family":"Xinyi","sequence":"first","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"},{"name":"Department of Stomatology Qingdao Special Servicemen Recuperation Center of PLA Navy  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tingting","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Xiaoyu","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hao","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qingchun","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Wei","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Yuhe","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Keke","sequence":"additional","affiliation":[{"name":"College &amp; Hospital of Stomatology Anhui Medical University, Anhui Province Key Laboratory of Oral Diseases Research  Hefei 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