{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:15:11Z","timestamp":1787724911803,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81500292"],"award-info":[{"award-number":["81500292"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["2015ZDTD044"],"award-info":[{"award-number":["2015ZDTD044"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon\u2010like peptide\u20101 (\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101 analog exendin\u20104 and the dipeptidyl peptidase\u20104 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (\n                    <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content>\n                    ). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in\n                    <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content>\n                    by low streptozotocin doses and high\u2010fat diets were significantly reversed by exendin\u20104 and saxagliptin treatments for 8\u00a0weeks. We found that exendin\u20104 inhibited abnormal activation of the (\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    \u03b1)\u2010\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    36 pathway by stimulating protein kinase A (\n                    <jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>\n                    ) but suppressing the Rho\u2010associated protein kinase (\n                    <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>\n                    ) pathway in\n                    <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content>\n                    hearts, palmitic acid (\n                    <jats:styled-content style=\"fixed-case\">PA<\/jats:styled-content>\n                    )\u2010treated rat h9c2 cardiomyocytes (\n                    <jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>\n                    s), and isolated adult mouse CMs. Cardioprotection in\n                    <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content>\n                    mediated by exendin\u20104 was abolished by combination therapy with the\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    \u03b1 agonist wy\u201014643 but mimicked by\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    \u03b1 gene deficiency. Therefore, the\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    \u03b1 pathway accounted for the effects of exendin\u20104. This conclusion was confirmed in cardiac\u2010restricted overexpression of\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    \u03b1 mediated by adeno\u2010associated virus serotype\u20109 containing a cardiac troponin T promoter. Our results provide the first direct evidence that\n                    <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                    \u20101 protects cardiac function by inhibiting the\n                    <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n                    \u03b1 pathway, thereby ameliorating lipotoxicity in diabetic cardiomyopathy.\n                  <\/jats:p>","DOI":"10.1111\/acel.12763","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T11:50:30Z","timestamp":1523879430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Glucagon\u2010like peptide\u20101 ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via the\n                    <scp>PPAR<\/scp>\n                    \u03b1 pathway"],"prefix":"10.1111","volume":"17","author":[{"given":"Lujin","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neonatal Medicine The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wen","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology 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