{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:32:34Z","timestamp":1791649954780,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009383","name":"Tzu Chi University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myocardial hypertrophy is associated with a significant increase in intracellular Ca<jats:sup>2+<\/jats:sup>, which can be induced by long\u2010chain fatty acid. Palmitic acid methyl ester (PAME), a fatty acid ester released from adipose tissue, superior cervical ganglion, and retina, has been found to have anti\u2010inflammation, antifibrosis, and peripheral vasodilation effects. However, the effects of PAME on cardiomyocytes are still unclear. The aim of this study was to determine whether PAME could disrupt the intracellular Ca<jats:sup>2+<\/jats:sup> balance, leading to cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were treated with various concentrations (10\u2013100\u2009\u03bcM) of PAME for 1\u20134 days. Cytosolic Ca<jats:sup>2+<\/jats:sup> and mitochondrial Ca<jats:sup>2+<\/jats:sup> concentrations were examined using Fura\u20102 AM and Rhod\u20102, respectively. After treatment with PAME for 4 days, mitochondrial Ca<jats:sup>2+<\/jats:sup>, an indicator of the state of mitochondrial permeability transition pore (MPTP), and cell death were monitored by flow cytometric analysis. ATP levels were detected using the ATP assay kit. Cardiomyocyte hypertrophy was analyzed by measuring the cardiac hypertrophy biomarker and cell area\u00a0using quantitative real time\u2010polymerase chain reaction, Western Blot analysis and immunofluorescence analysis. Our results show that PAME concentration\u2010 and time\u2010dependently increased cytosolic and mitochondria Ca<jats:sup>2+<\/jats:sup> through the mitochondrial calcium uniporter. Moreover, treatment with PAME for 4 days caused MPTP opening, thereby reducing ATP production and enhancing reactive oxygen species (ROS) generation, and finally led to cardiomyocyte hypertrophy. These effects caused by PAME treatment were attenuated by the G\u2010protein coupled receptor 40 (GPR40) inhibitor. In conclusion, PAME impaired mitochondrial function, which in turn led to cardiomyocyte hypertrophy through increasing the mitochondrial Ca<jats:sup>2+<\/jats:sup> levels mediated by activating the GPR40 signaling pathway.<\/jats:p>","DOI":"10.1002\/jcp.30922","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T19:30:32Z","timestamp":1671564632000},"page":"242-256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Palmitic acid methyl ester induces cardiac hypertrophy through activating the GPR receptor\u2010mediated changes of intracellular calcium concentrations and mitochondrial functions"],"prefix":"10.1002","volume":"238","author":[{"given":"Chih\u2010Feng","family":"Lien","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences, College of Medicine Tzu Chi University Hualien Taiwan"},{"name":"Department of Medicine, Division of Cardiology, Tri\u2010Service 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