{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:40:47Z","timestamp":1777945247785,"version":"3.51.4"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Palmitoylethanolamide (PEA) is an endogenous lipid mediator with immunomodulatory actions, yet its effects in skeletal muscle remain poorly defined. We examined whether PEA influences myogenesis and profiled the acute transcriptomic response of differentiated C2C12 myotubes to 10\u2009\u03bcM PEA. PEA decreased myotube number (90.3\u2009\u00b1\u200910.6 vs. 112.6\u2009\u00b1\u200910.1 control) while increasing nuclear fusion index (37.8\u2009\u00b1\u20095.7% vs. 30.7\u2009\u00b1\u20093.2%); myotube area was unchanged. In myoblasts, 24\u2009h PEA increased G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    (48.2\u2009\u00b1\u20091.2% vs. 42.3\u2009\u00b1\u20091.9%) and reduced S\u2010phase (21.7\u2009\u00b1\u20091.2% vs. 25.5\u2009\u00b1\u20091.2%), consistent with G\n                    <jats:sub>1<\/jats:sub>\n                    arrest. RNA sequencing identified 1952 differentially expressed genes enriched for cytokine\u2013receptor interactions and inflammatory signaling. PEA downregulated NF\u2010\u03baB target cytokines while upregulating interferon\u2010related and chemokine genes, indicating an anti\u2010inflammatory\/immune\u2010priming profile. N\u2010acylethanolamine acid amidase was highly expressed and induced, whereas fatty acid amide hydrolase remained low and unchanged, suggesting muscle\u2010specific reliance on NAAA metabolism. These data show that PEA biases skeletal muscle toward a less proliferative but more fused and inflammation\u2010resolving phenotype, with transcriptional reprogramming of immune pathways and preferential NAAA engagement. These findings motivate in\u00a0vivo studies to test whether such actions benefit muscle regeneration, adaptation, or anti\u2010atrophy interventions.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70780","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T07:28:37Z","timestamp":1771226917000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Palmitoylethanolamide (\n                    <scp>PEA<\/scp>\n                    ) regulates cell cycle progression and promotes an anti\u2010inflammatory transcriptomic signature in\n                    <scp>C2C12<\/scp>\n                    skeletal muscle cells"],"prefix":"10.14814","volume":"14","author":[{"given":"Paige L.","family":"Cole","sequence":"first","affiliation":[{"name":"Research Institute of Sport and Exercise Science (RISES) Liverpool John Moores University  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott H.","family":"Gillham","sequence":"additional","affiliation":[{"name":"Research Institute of Sport and Exercise Science (RISES) Liverpool John Moores University  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0722-7051","authenticated-orcid":false,"given":"Mark R.","family":"Viggars","sequence":"additional","affiliation":[{"name":"Department of Physiology and Aging University of Florida  Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graeme L.","family":"Close","sequence":"additional","affiliation":[{"name":"Research Institute of Sport and Exercise Science (RISES) Liverpool John Moores University  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-8677","authenticated-orcid":false,"given":"Daniel J.","family":"Owens","sequence":"additional","affiliation":[{"name":"Research Institute of Sport and Exercise Science (RISES) Liverpool John Moores University  Liverpool UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0782067"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901510RR"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00821"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.890855"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.36648\/nutraceuticals.5.2.3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/384083a0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.25"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063054"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014\u20105793(01)02934\u20109"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/328797"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13020"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526\u20104637.2012.01432.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22756"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2005.04.018"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062741"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","unstructured":"Iannotti F. 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Di Marzo V. &Petrosino S.(2016).Endocannabinoids and endocannabinoid\u2010related mediators: Targets metabolism and role in neurological disorders.","DOI":"10.1016\/j.plipres.2016.02.002"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010014\u20100136\u20100"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010008\u20100373\u20108"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.01.021"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.006353"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081923"},{"issue":"2","key":"e_1_2_9_24_1","first-page":"11","article-title":"Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: A pooled data meta\u2010analysis","volume":"19","author":"Paladini A.","year":"2016","journal-title":"Pain Physician"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13580"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1671-5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.0c02903"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010015\u20109253\u20108"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2018.02.005"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413473200"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2010.02.003"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22056"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70780","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.70780","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70780","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:37:37Z","timestamp":1777718257000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.70780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.14814\/phy2.70780"],"URL":"https:\/\/doi.org\/10.14814\/phy2.70780","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70780"}}