{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:44:34Z","timestamp":1788716674535,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["963419"],"award-info":[{"award-number":["963419"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["22406"],"award-info":[{"award-number":["22406"]}],"id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013465","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["23737"],"award-info":[{"award-number":["23737"]}],"id":[{"id":"10.13039\/100013465","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple signaling pathways have been reported to be altered in Myotonic Dystrophy type 1 (DM1) skeletal muscle, contributing to pathogenicity. In particular, previous work established that AMPK signaling, a key sensor of energy metabolism, is repressed in DM1 mouse muscle and that activating AMPK through exercise and\/or with pharmacological activators is beneficial for the DM1 muscle phenotype. Here, we explored the effects of a newer, more specific allosteric AMPK activator acting directly on AMPK. We treated male and female HSA\n                    <jats:sup>LR<\/jats:sup>\n                    mice for 1 and 4\u2009weeks with a daily injection of the allosteric activator MK\u20108722, the AMP mimetic AICAR, or vehicle. Our results show that 1 and 4\u2009weeks of treatment with MK\u20108722 improves alternative splicing toward wild\u2010type levels in male and female HSA\n                    <jats:sup>LR<\/jats:sup>\n                    muscle. However, the effects of MK\u20108722 were more modest compared to AICAR. In contrast, 4\u2009weeks of treatment with MK\u20108722 improved muscle histology to a greater extent than AICAR. As expected with AMPK activation, 4\u2009weeks of treatment with MK\u20108722 and AICAR promoted the expression of slower, more oxidative fibers. Finally, acute injections of MK\u20108722 and AICAR triggered the rapid and transient increase in phospho\u2010AMPK in muscle. However, the peak of AMPK phosphorylation was lower with MK\u20108722 compared to AICAR, thereby explaining the more modest effects of AMPK allosteric activation. Altogether, our data demonstrate that chronic activation of AMPK with specific pharmacological activators is beneficial for the DM1 muscle. They further indicate that at least a portion of the beneficial effects seen following the administration of these drugs occurs through AMPK.\n                  <\/jats:p>","DOI":"10.1096\/fj.202401145rr","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T05:39:08Z","timestamp":1732858748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The\n                    <scp>AMPK<\/scp>\n                    allosteric activator\n                    <scp>MK<\/scp>\n                    \u20108722 improves the\u00a0histology and spliceopathy in myotonic dystrophy type\u00a01\u00a0(\n                    <scp>DM1<\/scp>\n                    ) skeletal muscle"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-7372","authenticated-orcid":false,"given":"Aymeric","family":"Ravel\u2010Chapuis","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"The Eric Poulin Centre for Neuromuscular Disease University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8071-6944","authenticated-orcid":false,"given":"Chim\u00e8ne","family":"Fahmi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"The Eric Poulin Centre for Neuromuscular Disease University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0186-4213","authenticated-orcid":false,"given":"Jonathan","family":"Gobin","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"The Eric Poulin Centre for Neuromuscular Disease University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5798-4475","authenticated-orcid":false,"given":"Bernard J.","family":"Jasmin","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"The Eric Poulin Centre for Neuromuscular Disease University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.05.017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000369343"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90154-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1546326"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1546325"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2014.04.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0692-192"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11091109"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12674"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2015.02.009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy245"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI156125"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP282725"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89616"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac222"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy231"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277123"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-019-2458-7"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.163856"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051095"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5582"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0211568"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100496"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00237.2016"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.04.010"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072092"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01018-x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91191-6"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5485.1769"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148264"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.04.007"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202401145RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:59:47Z","timestamp":1761681587000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202401145RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,29]]},"references-count":31,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,12,15]]}},"alternative-id":["10.1096\/fj.202401145RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202401145rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,29]]},"assertion":[{"value":"2024-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70199"}}