{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:10:00Z","timestamp":1788570600382,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcopenic obesity, where excess body fat coexists with reduced muscle mass and function, is becoming increasingly common in ageing populations and contributes to poor physical and metabolic health. Although adipose tissue\u2013secreted factors are implicated in muscle decline, the specific mechanisms remain unclear. Extracellular vesicles (EVs), which carry regulatory cargo such as microRNAs (miRNAs) between cells, may play a key role in this adipose\u2013muscle communication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      EVs were isolated from adipose\u2010conditioned media (ACM) collected from lean and non\u2010lean human donors using ultracentrifugation. Donors were grouped by BMI (lean: 20.7\u201324.4; non\u2010lean: 25.3\u201339.3) and age (younger: 31\u201356\u2009years; older: 60\u201384\u2009years). EVs were characterised using nanoparticle tracking analysis (NTA), ExoView, nanoscale flow cytometry (CytoFLEX Nano) and transmission electron microscopy (TEM). Primary human myoblasts were differentiated into myotubes and treated for 24\u2009h with lean or non\u2010lean EVs (1.3\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      particles\/mL) or left untreated. Myotube thickness was measured by immunofluorescence microscopy. Transcriptomic changes were assessed by bulk RNA sequencing. EV miRNA cargo was profiled by small RNA\u2010seq and validated by qPCR. The role of miR\u2010150\u20105p was tested using antagomir inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Non\u2010lean EVs significantly reduced myotube thickness in older adult\u2010derived myotubes compared to both untreated controls (8.7\u2009\u00b1\u20091.66\u2009\u03bcm vs. 12.4\u2009\u00b1\u20091.72\u2009\u03bcm,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and lean EV\u2010treated myotubes (8.7\u2009\u00b1\u20091.66\u2009\u03bcm vs. 13.2\u2009\u00b1\u20093.84\u2009\u03bcm,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), indicating a donor BMI\u2010specific effect. This atrophy was restricted to myotubes derived from older donors. The same experimental approach was applied to younger adult\u2010derived myotubes; no reduction in myotube thickness was observed.\n                    <\/jats:p>\n                    <jats:p>\n                      MAFbx expression was significantly increased in response to non\u2010lean EVs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). RNA\u2010seq revealed 471 differentially expressed genes (DEGs) in EV\u2010treated versus untreated cells and 293 DEGs between lean and non\u2010lean EV conditions, with enrichment in inflammatory (TNF and IL1B), oxidative stress, mitochondrial and chromatin pathways. Small RNA\u2010seq identified seven differentially expressed miRNAs (annotated using miRBase release 22.1), including miR\u2010150\u20105p and miR\u2010193b\u20105p, both significantly upregulated in non\u2010lean EVs and validated by qPCR. Inhibiting miR\u2010150\u20105p partially rescued myotube thickness (10.5\u2009\u00b1\u20091.37\u2009\u03bcm vs. 8.7\u2009\u00b1\u20091.66\u2009\u03bcm,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and reduced MAFbx expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EVs from non\u2010lean adipose tissue drive muscle atrophy and transcriptional changes in an age\u2010dependent manner. These effects are partially mediated by miR\u2010150\u20105p, highlighting a mechanistic role for EV cargo in adipose\u2010muscle signalling. Targeting EV\u2010derived miRNAs may offer a novel strategy to combat muscle loss in obesity and ageing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70204","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:40:09Z","timestamp":1770129609000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Obesity Reprogrammes Adipose Extracellular Vesicles to Induce Muscle Atrophy via miR\u2010150\u20105p\u2010Mediated Transcriptional Silencing"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9950-7992","authenticated-orcid":false,"given":"Joshua\u00a0M.\u00a0J.","family":"Price","sequence":"first","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Department of Inflammation and Ageing, School of Infection, Inflammation &amp; Immunology, College of Medicine and Health University of Birmingham  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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Lachlan\u2010Jiraskova","sequence":"additional","affiliation":[{"name":"School of Biological and Medical Sciences Oxford Brookes University, Headington Campus  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward\u00a0T.","family":"Davis","sequence":"additional","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Department of Inflammation and Ageing, School of Infection, Inflammation &amp; Immunology, College of Medicine and Health University of Birmingham  Birmingham UK"},{"name":"Royal Orthopaedic Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostas","family":"Tsintzas","sequence":"additional","affiliation":[{"name":"MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences University of Nottingham, Queen's Medical Centre  Nottingham 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