{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:45:11Z","timestamp":1792622711119,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The current study was designed to identify the effects of EAT\u2010derived leptin on the myocardium of MetS rats and explore the potential molecular mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              A MetS rat model was established in 8\u2010week\u2010old Wistar rats by a 12\u2010week high\u2010fat diet. MetS rats exhibited increased leptin secretion from EAT, cardiac hypertrophy, and diastolic dysfunction with preserved systolic function. The myocardium of MetS rats had abnormal structure, increased oxidative stress injury, and higher inflammatory factor levels, especially the subepicardial myocardium, which was correlated with the EAT\u2010derived leptin level but not the serum leptin. The EAT was separated from each group of rats to prepare EAT\u2010conditioned medium. H9C2 rat cardiomyoblasts were treated with EAT\u2010conditioned medium or leptin, plus various inhibitors. EAT\u2010derived leptin from MetS rats promoted mitochondrial oxidative stress and dysfunction, induced mitochondrial pathway apoptosis, and inhibited cell viability in H9C2 cardiomyoblasts via the protein kinase C\/reduced nicotinamide adenine dinucleotide phosphate oxidase\/reactive oxygen species (PKC\/NADPH oxidase\/ROS) pathway. EAT\u2010derived leptin from MetS rats stimulated inflammation in H9C2 cardiomyocytes by promoting activator protein 1 nuclear translocation via the PKC\/NADPH oxidase\/ROS pathway. Leptin promoted the interaction between p\u2010p47\n              <jats:sup>phox<\/jats:sup>\n              and gp91\n              <jats:sup>phox<\/jats:sup>\n              in H9C2 cardiomyocytes via protein kinase C, activating nicotinamide adenine dinucleotide phosphate oxidase, increasing reactive oxygen species generation, and inhibiting cell viability.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">EAT\u2010derived leptin induces MetS\u2010related myocardial injury through the following 2 cooperative ways via PKC\/NADPH oxidase\/ROS pathway: (1) inducing mitochondrial pathway apoptosis by promoting mitochondrial oxidative stress and dysfunction; and (2) stimulating inflammation by promoting activator protein 1 nuclear translocation.<\/jats:p>\n          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