{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:57:50Z","timestamp":1790877470476,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Metabolic syndrome (MetS) is a major contributor to cardiovascular disease and is characterized by impaired Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling and mitochondrial dysfunction in cardiomyocytes. However, the upstream mechanisms linking metabolic stress to these alterations remain incompletely defined. Here, we investigated whether sirtuin signalling coordinates intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis and mitochondrial function in a high\u2010sucrose diet\u2010induced mouse model of MetS. Male BALB\/c mice were exposed to 32% sucrose for 24\u00a0weeks, followed by isolation of ventricular cardiomyocytes. MetS cardiomyocytes exhibited mitochondrial depolarization, increased reactive oxygen species production, elevated basal cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels, reduced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient amplitude and decreased sarcoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    content. These alterations were associated with reduced phospholamban phosphorylation, increased CaMKII and ryanodine receptor phosphorylation and activation of pro\u2010apoptotic signalling. Notably, pharmacological inhibition of SIRT1 with EX527 in control cardiomyocytes recapitulated key features of the MetS phenotype, whereas SIRT1 activation with SRT1720 restored mitochondrial membrane potential, reduced reactive oxygen species production, improved Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling, normalized aberrant phosphorylation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010handling proteins and attenuated apoptotic signalling. Collectively, these findings identify SIRT1 as a critical integrator of mitochondrial function and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis during metabolic stress, highlighting sirtuin\u2010dependent pathways as promising therapeutic targets in metabolic cardiomyopathy.\n                  <\/jats:p>","DOI":"10.1113\/ep094062","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:50:21Z","timestamp":1785819021000},"page":"4646-4658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sirtuin signalling governs calcium homeostasis and mitochondrial function in metabolic syndrome cardiomyocytes"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1609-6847","authenticated-orcid":false,"given":"Firat","family":"Akat","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Ankara 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Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-2534","authenticated-orcid":false,"given":"Erkan","family":"Tuncay","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine Ankara University  Ankara Turkiye"},{"name":"Department of Interdisciplinary Neuroscience, Faculty of Medicine  Ankara Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192644"},{"key":"e_1_2_11_3_1","volume-title":"Guide for the care and use of laboratory animals","author":"Albus 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