{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:10:42Z","timestamp":1791835842872,"version":"4.3.4"},"reference-count":84,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T00:00:00Z","timestamp":1706918400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170369"],"award-info":[{"award-number":["82170369"]}],"id":[{"id":"10.13039\/501100001809","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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. Here, we investigated in a cardiomyocyte\u2010restricted Nrf2 transgenic mice (Nrf2\u2010TG) the direct effect of Nrf2 on cardiomyocytes in DCM and its mechanism. In this study, cardiomyocyte\u2010restricted Nrf2 transgenic mice (Nrf2\u2010TG) were used to directly observe whether cardiomyocyte\u2010specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. Compared to wild\u2010type mice, Nrf2\u2010TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin\u2010induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. These results showed that Nrf2 can directly act on cardiomyocytes to exert a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by directly targeting lipid metabolic pathway of AMPK\/Sirt1\/PGC\u20101\u03b1 activation via upstream genes of sestrin2 and LKB1, and indirectly enabling AKT\/GSK\u20103\u03b2\/HK\u2010\u2161 activity via AMPK mediated p70S6K inhibition.<\/jats:p>","DOI":"10.1002\/jcp.31149","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T12:23:10Z","timestamp":1706962990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nrf2 prevents diabetic cardiomyopathy via antioxidant effect and normalization of glucose and lipid metabolism in the heart"],"prefix":"10.1002","volume":"239","author":[{"given":"Ge","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences Jilin University Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences Jilin University Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences Jilin University Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowen","family":"Hou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences Jilin University Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjie","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of 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