{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:38:13Z","timestamp":1780447093126,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long\u2010term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13\u2010week\u2010old C57BL\/6J wild\u2010type and myostatin knock\u2010out male mice. Survival rates were similar in wild\u2010type and myostatin knock\u2010out mice seven days after CLP. Loss in muscle mass was also similar in wild\u2010type and myostatin knock\u2010out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3\u2010ubiquitin ligases and autophagy\u2013lysosome markers. This transcriptional response was blunted in myostatin knock\u2010out mice. No change was observed in the protein level of markers of the anabolic insulin\/IGF1\u2010Akt\u2010mTOR pathway. Muscle strength was similarly decreased in wild\u2010type and myostatin knock\u2010out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation\u2013contraction coupling, suggesting that a long\u2010term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation\u2013contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16106-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Survival rates are similar in wild\u2010type and myostatin knock\u2010out mice seven days after the induction of sepsis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Loss in muscle mass and muscle strength are similar in wild\u2010type and myostatin knock\u2010out mice 4 and 7 days after the induction of an experimental sepsis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin\/IGF1\u2010Akt\u2010mTOR pathway remained unchanged.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RT\u2010qPCR analysis of autophagy\u2013lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild\u2010type and myostatin knock\u2010out mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Experimental sepsis induces greater variations in the mRNA levels of wild\u2010type mice than those of myostatin knock\u2010out mice, without providing any significant catabolic resistance or functional benefits.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284973","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T16:09:48Z","timestamp":1715789388000},"page":"2839-2854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Myostatin gene invalidation does not prevent skeletal muscle mass loss during experimental sepsis in mice"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-6776","authenticated-orcid":false,"given":"J\u00e9rome","family":"Morel","sequence":"first","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"},{"name":"D\u00e9partement d'anesth\u00e9sie et r\u00e9animation Centre Hospitalier Universitaire de Saint Etienne  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2703-9295","authenticated-orcid":false,"given":"Anne Sophie","family":"Pignard","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"},{"name":"D\u00e9partement d'anesth\u00e9sie et r\u00e9animation Centre Hospitalier Universitaire de Saint Etienne  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane","family":"Castells","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Allibert","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9796-8604","authenticated-orcid":false,"given":"Lahc\u00e8ne","family":"Hatimi","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Buhot","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Velarde","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C\u00e9cile","family":"Durieux","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Freyssenet","sequence":"additional","affiliation":[{"name":"Laboratoire Interuniversitaire de Biologie de la Motricit\u00e9 Universit\u00e9 Jean Monnet Saint Etienne, Lyon 1, Universit\u00e9 Savoie Mont\u2010Blanc  Saint Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200712-1829OC"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0959"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1256804"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13104"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.206193"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.160150"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.008574"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1500"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00668.2005"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00028.2014"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0057"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10188"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-022-04101-1"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022450"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000854"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3552"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110233"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00161.2020"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15153"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70178-8"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-012422-112116"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01486-4"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/387083a0"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047265"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11440-5"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49920"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.278481"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-010-0010-6"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040933"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-022-06819-6"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118586"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00341.2004"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0245"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics10080574"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-014-3224-9"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-176917"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.07.011"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP284973","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T06:52:41Z","timestamp":1718347961000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP284973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1113\/JP284973"],"URL":"https:\/\/doi.org\/10.1113\/jp284973","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"assertion":[{"value":"2023-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}