{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:59:23Z","timestamp":1785257963153,"version":"3.55.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The favorable cardiovascular effects of sodium\u2013glucose co\u2010transporter 2 inhibitors in diabetes are well established, but their potential to ameliorate obesity\u2010related cardiac dysfunction remains unclear. Pericardial adipose tissue (PAT)\u2010derived adipocytokines, particularly leptin, contribute to obesity\u2010associated cardiac remodeling. We investigated the detrimental effects of PAT\u2010derived leptin on cardiac remodeling and whether dapagliflozin confers cardioprotection by reducing and counteracting PAT\u2010derived leptin in obese rodents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Male Wistar rats, C57BL\/6J mice, and ob\/ob mice were fed a normal or high\u2010fat diet for 20\u2009weeks, with or without dapagliflozin (1 mg\/kg per day) for the final 8\u2009weeks. PAT adipocytes from 8\u2010week\u2010old rats were isolated and induced to insulin resistance. Primary cardiac fibroblasts and cardiomyocytes were exposed to PAT\u2010conditioned medium, leptin antagonist, dapagliflozin (10 \u03bcM), reactive oxygen species scavenger N\u2010acetylcysteine (50\u2009mM), pNaKtide (10 \u03bcM), Src inhibitor PP2 (10 \u03bcM). Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase expression and activity, mitochondrial membrane potential, and mitochondrial permeability transition pore opening were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The intervention of dapagliflozin to high\u2010fat diet\u2013fed Wistar rats could reduce body weight and improve metabolic disorders. Furthermore, dapagliflozin significantly alleviated the adipocyte hypertrophy of PAT, cardiac fibrosis and apoptosis, as well as the leptin production and secretion from PAT. In\u00a0vitro, dapagliflozin inhibits the leptin production and secretion in insulin\u2010resistant adipocytes of PAT by regulating the phosphoinositide 3\u2010kinase\/protein kinase B and extracellular signal\u2010regulated kinase 1\/2 signaling pathway. Meanwhile, dapagliflozin could counteract the profibrotic effect of PAT\u2010derived leptin via inhibiting the signal transducer and activator of transcription 3\u2013reactive oxygen species\/Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase\/Src oxidative stress loop signaling pathway. Meanwhile, dapagliflozin could also attenuate cardiomyocytes apoptosis induced by PAT\u2010derived leptin via suppressing Janus kinase 2\/signal transducer and activator of transcription 3\u2010Bax and inhibiting reactive oxygen species\/Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase\/Src oxidative stress loop.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Dapagliflozin reduced PAT\u2010derived leptin via phosphoinositide 3\u2010kinase\/protein kinase B and extracellular signal\u2010regulated kinase 1\/2 signaling and mitigated PAT\u2010derived leptin\u2010induced myocardial fibrosis and apoptosis by inhibiting signal transducer and activator of transcription 3\u2010mediated reactive oxygen species\/Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010K\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase\/Src oxidative stress signaling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.048155","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T10:59:07Z","timestamp":1784285947000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Dapagliflozin Attenuates Pericardial Adipose Tissue\u2013Derived Leptin\u2010Mediated Myocardial Remodeling in Obese Rats"],"prefix":"10.1161","volume":"15","author":[{"given":"Chaodi","family":"Luo","sequence":"first","affiliation":[{"name":"First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, People\u2019s Republic of 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