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Muscle glycogen and lactate extrusion are critical for physical performance. The mechanism by which glycogen and lactate metabolism are manipulated during exercise remains unclear. This study aimed to assess the effect of miR\u201092b on the upregulation of exercise training\u2010induced physical performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adeno\u2010associated virus (AAV)\u2010mediated skeletal muscle miR\u201092b overexpression in C57BLKS\/J mice, and global knockout of miR\u201092b mice were used to explore the function of miR\u201092b in glycogen and lactate metabolism in skeletal muscle. AAV\u2010mediated UGP2 or MCT4 knockdown in WT or miR\u201092 knockout mice was used to confirm whether miR\u201092b regulates glycogen and lactate metabolism in skeletal muscle through UGP2 and MCT4. Body weight, muscle weight, grip strength, running time and distance to exhaustion, and muscle histology were assessed. The expression levels of muscle mass\u2010related and function\u2010related proteins were analysed by immunoblotting or immunostaining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Global knockout of miR\u201092b resulted in normal body weight and insulin sensitivity, but higher glycogen content before exercise exhaustion (0.8538\u00a0\u00b1\u00a00.0417 vs. 1.043\u00a0\u00b1\u00a00.040, **<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0087), lower lactate levels after exercise exhaustion (4.133\u00a0\u00b1\u00a00.2589 vs. 3.207\u00a0\u00b1\u00a00.2511, *<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0279), and better exercise capacity (running distance to exhaustion, 3616\u00a0\u00b1\u00a086.71 vs. 4231\u00a0\u00b1\u00a090.29, ***<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0006; running time to exhaustion, 186.8\u00a0\u00b1\u00a08.027 vs. 220.8\u00a0\u00b1\u00a03.156, **<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0028), as compared with those observed in the control mice. Mice skeletal muscle overexpressing miR\u201092b (both miR\u201092b\u20103p and miR\u201092b\u20105p) displayed lower glycogen content before exercise exhaustion (0.6318\u00a0\u00b1\u00a00.0231 vs. 0.535\u00a0\u00b1\u00a00.0194, **<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0094), and higher lactate accumulation after exercise exhaustion (4.5\u00a0\u00b1\u00a00.2394 vs. 5.467\u00a0\u00b1\u00a00.1892, *<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01), and poorer exercise capacity (running distance to exhaustion, 4005\u00a0\u00b1\u00a081.65 vs. 3228\u00a0\u00b1\u00a0149.8, ***<jats:italic>P<\/jats:italic>&lt;0.0001; running time to exhaustion, 225.5\u00a0\u00b1\u00a07.689 vs. 163\u00a0\u00b1\u00a06.476, **<jats:italic>P<\/jats:italic>\u00a0=\u00a00.001). Mechanistic analysis revealed that miR\u201092b\u20103p targets UDP\u2010glucose pyrophosphorylase 2 (UGP2) expression to inhibit glycogen synthesis, while miR\u201092b\u20105p represses lactate extrusion by directly target monocarboxylate transporter 4 (MCT4). Knockdown of UGP2 and MCT4 reversed the effects observed in the absence of miR\u201092b in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study revealed regulatory pathways, including miR\u201092b\u20103p\/UGP2\/glycogen synthesis and miR\u201092b\u20105p\/MCT4\/lactate extrusion, which could be targeted to control exercise capacity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13377","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T22:42:28Z","timestamp":1700606548000},"page":"2925-2938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MicroRNA\u201092b in the skeletal muscle regulates exercise capacity via modulation of glucose metabolism"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4912-777X","authenticated-orcid":false,"given":"Shu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College Jinan University  Guangzhou China"},{"name":"The First Affiliated Hospital Southern University of Science and Technology  Shenzhen China"},{"name":"Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College Jinan University  Guangzhou China"},{"name":"Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College Jinan University  Guangzhou China"},{"name":"Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College Jinan University  Guangzhou China"},{"name":"Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's Hospital  Shenzhen 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