{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:02:31Z","timestamp":1789970551350,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["isevjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Bio"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Recent studies have shown that adipose tissue (AT) secretes elevated levels of extracellular vesicles (EVs) in obesity, and these EVs play roles in metabolic diseases. The inhibition of calpains has anti\u2010inflammatory and anti\u2010fibrotic effects on AT in mice and reduces EV secretion in some cell types in vitro. However, its effects on human AT and adipocyte EV secretion remain unexplored. This study aimed to investigate calpeptin's effects on EV\u2010mediated communication and adipocyte function, offering potential insights into therapeutic approaches for metabolic diseases. Human Simpson Golabi Behmel Syndrome (SGBS) preadipocytes were differentiated and treated with calpeptin. EVs were isolated by standard ultracentrifugation, and studied by nanoparticle tracking analysis, electron microscopy, and mass spectrometry. Diverse analyses, including RNA\u2010sequencing, liquid chromatography\u2013mass spectrometry (LC\u2013MS), and confocal microscopy were utilized to study calpeptin's effects on SGBS cells. AT samples from bariatric surgery patients were cultured ex vivo to assess calpeptin's effects on primary AT. We demonstrated for the first time that calpeptin reduces EV secretion in human SGBS adipocytes. Proteomic analyses revealed that calpeptin alters the abundances of proteins related to EV secretory pathways. While reduced EV secretion was accompanied by anti\u2010inflammatory effects, calpeptin also altered insulin signalling pathways and reduced adiponectin expression, suggesting negative effects on adipocyte metabolism. Indeed, LC\u2013MS analyses of cells and EVs revealed that calpeptin altered proteins\u2014both in cells and EVs\u2014that are associated with stress responses. Notably, calpeptin upregulated HO\u20101 in vitro and in ex vivo AT cultures, indicating induced oxidative stress in adipocytes and AT. While calpeptin shows anti\u2010inflammatory promise in human SGBS adipocytes, its adverse effects on insulin signalling, adiponectin expression, and signs of oxidative stress raise concerns about its therapeutic potential against obesity\u2010related pathologies in humans. Our results highlight the need to understand the broader impact of calpeptin on adipocyte metabolism.<\/jats:p>","DOI":"10.1002\/jex2.70177","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:32:01Z","timestamp":1788028321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calpeptin Reduces Extracellular Vesicle Secretion and Induces Anti\u2010Inflammatory Effects but Upregulates HO\u20101 and Alters Adiponectin Levels in Human Adipocytes"],"prefix":"10.1002","volume":"5","author":[{"given":"Johanna","family":"Matilainen","sequence":"first","affiliation":[{"name":"Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine University of Helsinki Helsinki Finland"},{"name":"Institute of Biomedicine, School of Medicine, Faculty of Health Sciences University of Eastern Finland Kuopio 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