{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:52:22Z","timestamp":1791316342506,"version":"4.3.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M712119"],"award-info":[{"award-number":["2022M712119"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["WK9110000143"],"award-info":[{"award-number":["WK9110000143"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n It is well known that muscle disuse atrophy is associated with mitochondrial dysfunction, which is implicated in reduced nicotinamide adenine dinucleotide (NAD\n +<\/jats:sup>\n ) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate\u2010limiting enzyme in NAD\n +<\/jats:sup>\n biosynthesis, may serve as a novel strategy to treat muscle disuse atrophy by reversing mitochondrial dysfunction.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n To investigate the effects of NAMPT on the prevention of disuse atrophy of skeletal muscles predominantly composed of slow\u2010twitch (type I) or fast\u2010twitch (type II) fibres, rabbit models of rotator cuff tear\u2010induced supraspinatus muscle atrophy and anterior cruciate ligament (ACL) transection\u2010induced extensor digitorum longus (EDL) atrophy were established and then administered NAMPT therapy. Muscle mass, fibre cross\u2010sectional area (CSA), fibre type, fatty infiltration, western blot, and mitochondrial function were assayed to analyse the effects and molecular mechanisms of NAMPT in preventing muscle disuse atrophy.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Acute disuse of the supraspinatus muscle exhibited significant loss of mass (8.86\u00a0\u00b1\u00a00.25 to 5.10\u00a0\u00b1\u00a00.79\u00a0g;\n P<\/jats:italic>\n \u00a0<\u00a00.001) and decreased fibre CSA (3939.6\u00a0\u00b1\u00a0136.1 to 2773.4\u00a0\u00b1\u00a0217.6\u00a0\u03bcm\n 2<\/jats:sup>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.001), which were reversed by NAMPT (muscle mass 6.17\u00a0\u00b1\u00a00.54\u00a0g,\n P<\/jats:italic>\n \u00a0=\u00a00.0033; fibre CSA, 3219.8\u00a0\u00b1\u00a0289.4\u00a0\u03bcm\n 2<\/jats:sup>\n ,\n P<\/jats:italic>\n \u00a0=\u00a00.0018). Disuse\u2010induced impairment of mitochondrial function were significantly improved by NAMPT, including citrate synthase activity (40.8\u00a0\u00b1\u00a06.3 to 50.5\u00a0\u00b1\u00a05.6\u00a0nmol\/min\/mg,\n P<\/jats:italic>\n \u00a0=\u00a00.0043), and NAD\n +<\/jats:sup>\n biosynthesis (279.9\u00a0\u00b1\u00a048.7 to 392.2\u00a0\u00b1\u00a043.2\u00a0pmol\/mg,\n P<\/jats:italic>\n \u00a0=\u00a00.0023). Western blot revealed that NAMPT increases NAD\n +<\/jats:sup>\n levels by activating NAMPT\u2010dependent NAD\n +<\/jats:sup>\n salvage synthesis pathway. In supraspinatus muscle atrophy due to chronic disuse, a combination of NAMPT injection and repair surgery was more effective than repair in reversing muscle atrophy. Although the predominant composition of EDL muscle is fast\u2010twitch (type II) fibre type that differ from supraspinatus muscle, its mitochondrial function and NAD\n +<\/jats:sup>\n levels are also susceptible to disuse. Similar to the supraspinatus muscle, NAMPT\u2010elevated NAD\n +<\/jats:sup>\n biosynthesis was also efficient in preventing EDL disuse atrophy by reversing mitochondrial dysfunction.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n NAMPT\u2010elevated NAD\n +<\/jats:sup>\n biosynthesis can prevent disuse atrophy of skeletal muscles that predominantly composed with either slow\u2010twitch (type I) or fast\u2010twitch (type II) fibres by reversing mitochondrial dysfunction.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13182","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T23:10:20Z","timestamp":1677798620000},"page":"1003-1018","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Nicotinamide Phosphoribosyltransferase\u2010elevated NAD\n +<\/sup>\n biosynthesis prevents muscle disuse atrophy by reversing mitochondrial dysfunction"],"prefix":"10.1002","volume":"14","author":[{"given":"Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Provincial Hospital of Anhui Medical University Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Provincial Hospital of Anhui Medical University Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Provincial Hospital of Anhui Medical University Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qichun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui 230001 China"},{"name":"Department of Orthopedics Affiliated Provincial Hospital of Anhui Medical University Hefei Anhui 230001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0310-4919","authenticated-orcid":false,"given":"Chongyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200233 China"},{"name":"Department of Orthopedics Shanghai Eighth People's Hospital Shanghai 200235 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20123-1"},{"key":"e_1_2_7_3_1","first-page":"93","article-title":"Irreparable rotator cuff tears: challenges and solutions","volume":"10","author":"Novi M","year":"2018","journal-title":"Orthop Res 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