{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:54:46Z","timestamp":1772798086901,"version":"3.50.1"},"reference-count":92,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008102","name":"Ministerium f\u00fcr L\u00e4ndliche Entwicklung, Umwelt und Landwirtschaft des Landes Brandenburg","doi-asserted-by":"publisher","award":["82DZD00302"],"award-info":[{"award-number":["82DZD00302"]}],"id":[{"id":"10.13039\/501100008102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Neurofibromatosis type 1 (NF1) is a multi\u2010organ disease caused by mutations in neurofibromin 1 (\n NF1<\/jats:italic>\n ). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1\u2010associated myopathy are mostly unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To dissect the function of\n Nf1<\/jats:italic>\n in muscle, we created muscle\u2010specific knockout mouse models for NF1, inactivating\n Nf1<\/jats:italic>\n in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analysed during prenatal and postnatal myogenesis and muscle growth.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Nf1\n Lbx1<\/jats:sup>\n and Nf1\n Myf5<\/jats:sup>\n animals showed only mild defects in prenatal myogenesis. Nf1\n Lbx1<\/jats:sup>\n animals were perinatally lethal, while Nf1\n Myf5<\/jats:sup>\n animals survived only up to approximately 25\u00a0weeks. A comprehensive phenotypic characterization of Nf1\n Myf5<\/jats:sup>\n animals showed decreased postnatal growth, reduced muscle size, and fast fibre atrophy. Proteome and transcriptome analyses of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High\u2010resolution respirometry confirmed enhanced oxidative metabolism in Nf1\n Myf5<\/jats:sup>\n muscles, which was concomitant to a fibre type shift from type 2B to type 2A and type 1. Moreover, Nf1\n Myf5<\/jats:sup>\n muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1\n Myf5<\/jats:sup>\n animals, in line with a drastic reduction of white, but not brown adipose tissue.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results demonstrate a cell autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross\u2010tissue communication and mobilization of lipid reserves.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.12632","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T01:48:10Z","timestamp":1603158490000},"page":"1758-1778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis"],"prefix":"10.1002","volume":"11","author":[{"given":"Xiaoyan","family":"Wei","sequence":"first","affiliation":[{"name":"Musculoskeletal Development and Regeneration Group, Institute of Chemistry and Biochemistry Freie Universit\u00e4t Berlin Berlin Germany"},{"name":"Development and Disease Group Max Planck Institute for Molecular Genetics Berlin 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for Human Nutrition Nuthetal Germany"},{"name":"Institute of Nutritional Science, Department of Molecular and Experimental Nutritional Medicine University of Potsdam Potsdam Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"B\u00f6rno","sequence":"additional","affiliation":[{"name":"Sequencing Core Unit Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Timmermann","sequence":"additional","affiliation":[{"name":"Sequencing Core Unit Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0170-868X","authenticated-orcid":false,"given":"David","family":"Meierhofer","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Core Unit Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4248-6366","authenticated-orcid":false,"given":"Andre","family":"Kleinridders","sequence":"additional","affiliation":[{"name":"Junior Research Group Central Regulation of Metabolism German Institute for Human Nutrition Nuthetal Germany"},{"name":"Institute of Nutritional Science, Department of Molecular and Experimental Nutritional Medicine University of Potsdam Potsdam Germany"},{"name":"German Center for Diabetes Research (DZD) M\u00fcnchen\u2010Neuherberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8726-185X","authenticated-orcid":false,"given":"Susanne","family":"Klaus","sequence":"additional","affiliation":[{"name":"Department of Physiology of Energy Metabolism German Institute for Human Nutrition Nuthetal Germany"},{"name":"Institute of Nutritional Science University of Potsdam Potsdam Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-5363","authenticated-orcid":false,"given":"Sigmar","family":"Stricker","sequence":"additional","affiliation":[{"name":"Musculoskeletal Development and Regeneration Group, Institute of Chemistry and Biochemistry Freie Universit\u00e4t Berlin Berlin Germany"},{"name":"Development and Disease Group Max Planck Institute for Molecular Genetics Berlin 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