{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:52:09Z","timestamp":1788576729594,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000223","name":"Muscular Dystrophy Canada","doi-asserted-by":"publisher","award":["681362"],"award-info":[{"award-number":["681362"]}],"id":[{"id":"10.13039\/501100000223","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":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Duchenne muscular dystrophy (DMD) is a life\u2010limiting neuromuscular disorder characterized by muscle weakness and wasting. Previous proof\u2010of\u2010concept studies demonstrate that the dystrophic phenotype can be mitigated with the pharmacological stimulation of AMP\u2010activated protein kinase (AMPK). However, first\u2010generation AMPK activators have failed to translate from bench to bedside due to either their lack of potency or toxic, off\u2010target effects. The identification of safe and efficacious molecules that stimulate AMPK in dystrophic muscle is of particular importance as it may broaden the therapeutic landscape for DMD patients regardless of their specific dystrophin mutation. Here, we demonstrate that a single dose of the next generation, orally\u2010bioactive AMPK agonist MK\u20108722 (MK) to mdx mice evoked skeletal muscle AMPK and extensive downstream stimulation within 12\u00a0h post\u2010treatment. Specifically, MK elicited a gene expression profile indicative of a more disease\u2010resistant slow, oxidative phenotype including increased peroxisome proliferator\u2010activated receptor \u0263 coactivator\u20101\u237a activity and utrophin levels. In addition, we observed augmented autophagy signaling downstream of AMPK, as well as elevations in critical autophagic genes such as\n                    <jats:italic>Map1lc3<\/jats:italic>\n                    and\n                    <jats:italic>Sqstm1<\/jats:italic>\n                    subsequent to the myonuclear accumulation of the master regulator of the autophagy gene program, transcription factor EB. Lastly, we show that pharmacological AMPK stimulation normalizes the expression of myogenic regulatory factors and amends activated muscle stem cell content in mdx muscle. Our results indicate that AMPK activation via MK enhances disease\u2010mitigating mechanisms in dystrophic muscle and prefaces further investigation on the chronic effects of novel small molecule AMPK agonists.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201846rr","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T04:03:43Z","timestamp":1680667423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Acute, next\u2010generation\n                    <scp>AMPK<\/scp>\n                    activation initiates a disease\u2010resistant gene expression program in dystrophic skeletal muscle"],"prefix":"10.1096","volume":"37","author":[{"given":"Sean Y.","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew 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