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However, the underlying mechanisms and effective therapeutic strategies remain poorly understood. M2 macrophages within skeletal muscle play an important role in tissue recovery following injury. This study aims to investigate the role of M2 macrophages derived transforming growth factor\u2010beta 1 (Tgf\u2010\u03b21) in regulation of skeletal muscle function under diet\u2010induced obese conditions.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n An CD206\n +<\/jats:sup>\n M2 macrophage\u2010specific Tgf\u2010\u03b21 gene knockout (Tgf\u2010\u03b21 KO) mouse model was generated by crossing CD206\u2010CreER\n T2<\/jats:sup>\n mice with Tgf\u2010\u03b21\n f\/f<\/jats:sup>\n mice, followed by tamoxifen administration to induce Tgf\u2010\u03b21 gene deletion. Mice were then placed on a high\u2010fat diet (HFD) for 12\u2009weeks to develop obesity\u2010induced skeletal muscle dysfunction. The study used multiple physiological and molecular analyses, including exercise tolerance, hanging time, grip strength, glucose and insulin tolerance tests, western blotting, RT\u2010qPCR and others.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The present findings demonstrated improved exercise performance, as evidenced by increased running distance twice (\n p<\/jats:italic>\n \u2009=\u20090.0008) in Tgf\u2010\u03b21 KO mice. Deletion of CD206\n +<\/jats:sup>\n M2 macrophage\u2010specific Tgf\u2010\u03b21 stimulates fibro\u2010adipogenic progenitors (FAPs), inducing Follistatin (\n Fst<\/jats:italic>\n ) expression by 1.70\u2010fold (\n p<\/jats:italic>\n \u2009=\u20090.04) and follistatin\u2010like protein 1 (\n Fstl1<\/jats:italic>\n ) by 2.60\u2010fold (\n p<\/jats:italic>\n \u2009=\u20090.01) in tibialis anterior (TA), thus enhancing myogenesis. The Tgf\u2010\u03b21 KO mice showed increased muscle fibre type I (\n Myh7<\/jats:italic>\n by 2.40\u2010fold,\n p<\/jats:italic>\n \u2009=\u20090.005), muscle fibre type IIa (\n Myh2<\/jats:italic>\n by 1.50\u2010fold,\n p<\/jats:italic>\n \u2009=\u20090.003), type IIx (\n Myh1<\/jats:italic>\n by 2.35\u2010fold,\n p<\/jats:italic>\n \u2009=\u20090.002) in soleus and type II (\n Myh4<\/jats:italic>\n by 1.76\u2010fold,\n p<\/jats:italic>\n \u2009=\u20090.02) in TA. In Tgf\u2010\u03b21 KO mice, insulin\u2010stimulated Akt phosphorylation was significantly increased in adipose tissue by 2.14\u2010fold (\n p<\/jats:italic>\n \u2009=\u20090.0003) and in the liver by 1.62\u2010fold (\n p<\/jats:italic>\n \u2009=\u20090.01). Besides, the Tgf\u2010\u03b21 KO mice showed increased circulating adiponectin by 1.23 fold (\n p<\/jats:italic>\n \u2009=\u20090.003), thereby activating the AMPK\/SIRT1\/PGC\u20101\u03b1 pathway with the phosphorylation level of AMPK\u03b1 increased by 1.5\u2010fold (\n p<\/jats:italic>\n \u2009=\u20090.02), and PGC1\u03b1 protein level increased by 2.2\u2010fold (p\u2009=\u20090.02) via increased\n AdipoR1<\/jats:italic>\n mRNA expression by 1.8\u2010fold in TA,\n p<\/jats:italic>\n \u2009=\u20090.0001 and by 1.8\u2010fold in soleus,\n p<\/jats:italic>\n \u2009=\u20090.01 in skeletal muscle, leading to improved mitochondrial function in skeletal muscle.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The CD206\n +<\/jats:sup>\n M2 macrophage\u2010specific Tgf\u2010\u03b21 deletion ameliorates obesity\u2010induced muscle dysfunction, potentially via two distinct mechanisms. Firstly, it enhances myogenesis by promoting FAP\u2010mediated expression of\n Fst<\/jats:italic>\n and\n Fstl1<\/jats:italic>\n , thereby augmenting myogenesis\u2010related gene expression in skeletal muscle. Secondly, it also induces adipocytes to produce and secrete adiponectin into the bloodstream, thereby enhancing mitochondrial function via the AMPK\/SIRT1\/PGC\u20101\u03b1 pathway.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70322","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:13:02Z","timestamp":1781849582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of Tgf\u2010\u03b21 From CD206\n +<\/sup>\n M2 Macrophages Ameliorates Obesity\u2010Induced Suppression of Myogenesis and AMPK Phosphorylation in Skeletal Muscle"],"prefix":"10.1002","volume":"17","author":[{"given":"Muhammad","family":"Bilal","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine University of Toyama Toyama Japan"},{"name":"Research Center for Pre\u2010Disease Science, Faculty of Education and Research Promotion University of Toyama 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