{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:58Z","timestamp":1787028478687,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP20K08435"],"award-info":[{"award-number":["JP20K08435"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP21K16099"],"award-info":[{"award-number":["JP21K16099"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP19K08592"],"award-info":[{"award-number":["JP19K08592"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SENSHIN Medical Research Foundation","award":["JP20K08435"],"award-info":[{"award-number":["JP20K08435"]}]},{"name":"SENSHIN Medical Research Foundation","award":["JP21K16099"],"award-info":[{"award-number":["JP21K16099"]}]},{"name":"SENSHIN Medical Research Foundation","award":["JP19K08592"],"award-info":[{"award-number":["JP19K08592"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia\u2013reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia\u2013reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.<\/jats:p>","DOI":"10.3390\/ijms23158373","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T23:37:29Z","timestamp":1659310649000},"page":"8373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia\u2013Reperfusion Injury in Diet-Induced Obesity"],"prefix":"10.3390","volume":"23","author":[{"given":"Yuhei","family":"Oi","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8980-881X","authenticated-orcid":false,"given":"Tomohisa","family":"Nagoshi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Yasutake","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotake","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kashiwagi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-7880","authenticated-orcid":false,"given":"Toshikazu D.","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Core Research Facilities for Basic Science, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2828-7229","authenticated-orcid":false,"given":"Michihiro","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Tokyo 105-8461, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Forte, M., Madonna, M., Schiavon, S., Valenti, V., Versaci, F., Zoccai, G.B., Frati, G., and Sciarretta, S. 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