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Low\u2010level light therapy (LLLT) or photobiomodulation exhibits beneficial effects on promoting muscular functions, regeneration, and recovery from exhausting exercise, although the underlying cellular mechanisms remain poorly understood. We found that hypoxia, a condition following anaerobic exercise, significantly impeded myotube differentiation from myoblasts. However, this adverse effect was blunted greatly by pre\u2010exposure of myoblast cells to a 980\u2009nm laser at 0.1\u00a0J\/cm<jats:sup>2<\/jats:sup>, resulting in almost nearly normal myotube differentiation. LLL pre\u2010treatment enhanced myotube formation by 80%, with a tubular diameter of 4.28\u2009\u00b1\u20090.11\u2009\u03bcm on average, representative of a 53.4% increase over sham light treatment. The normalized myoblast differentiation concurred with 68% more mitochondrial mass and myogenin expression over controls. Moreover, LLL pre\u2010treatment appeared to enhance glucose uptake, prevent energy metabolic switch from oxidative phosphorylation to glycolysis, and diminish lactate production under hypoxic conditions. The observation provides valuable guidance with respect to the timing of LLLT and its potential effects on muscle strengths in concert with anaerobic exercise.<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio202100246-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.202100246","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T12:29:35Z","timestamp":1636460975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Low\u2010level light pre\u2010conditioning promotes <scp>C2C12<\/scp> myoblast differentiation under hypoxic conditions"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0907-6741","authenticated-orcid":false,"given":"Min","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Dermatology Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-5283","authenticated-orcid":false,"given":"Mei X.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.02.004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/593267"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1591672"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-009-0697-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.12397"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.201400087"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2016.0332"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-020-02978-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04680.x"},{"issue":"3","key":"e_1_2_9_12_1","first-page":"223","volume":"48","author":"Burattini S.","year":"2004","journal-title":"Eur. 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