{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:26:13Z","timestamp":1790900773697,"version":"4.1.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070259"],"award-info":[{"award-number":["82070259"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330012"],"award-info":[{"award-number":["82330012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82220108021"],"award-info":[{"award-number":["82220108021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["22ZR1440700"],"award-info":[{"award-number":["22ZR1440700"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH Medical Scientist Training Program Training","award":["T32GM007739"],"award-info":[{"award-number":["T32GM007739"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association Predoctoral Fellowship","doi-asserted-by":"publisher","award":["101010"],"award-info":[{"award-number":["101010"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Adiponectin is an adipocyte-derived circulating protein that exerts cardiovascular and metabolic protection. Due to the futile degradation of endogenous adiponectin and the challenges of exogenous administration, regulatory mechanisms of adiponectin biosynthesis are of significant pharmacological interest.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Here, we report that 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) generated by inositol hexakisphosphate kinase 1 (IP6K1) governed circulating adiponectin levels via thiol-mediated protein quality control in the secretory pathway. IP6K1 bound to adiponectin and DsbA-L and generated 5-InsP7 to stabilize adiponectin\/ERp44 and DsbA-L\/Ero1-L\u03b1 interactions, driving adiponectin intracellular degradation. Depleting 5-InsP7 by either IP6K1 deletion or pharmacological inhibition blocked intracellular adiponectin degradation. Whole-body and adipocyte-specific deletion of IP6K1 boosted plasma adiponectin levels, especially its high molecular weight forms, and activated AMPK-mediated protection against myocardial ischaemia\u2013reperfusion injury. Pharmacological inhibition of 5-InsP7 biosynthesis in wild-type but not adiponectin knockout mice attenuated myocardial ischaemia\u2013reperfusion injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our findings revealed that 5-InsP7 is a physiological regulator of adiponectin biosynthesis that is amenable to pharmacological intervention for cardioprotection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae017","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T20:45:28Z","timestamp":1705956328000},"page":"954-970","source":"Crossref","is-referenced-by-count":13,"title":["Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischaemia\u2013reperfusion injury by elevating plasma adiponectin"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0059-5908","authenticated-orcid":false,"given":"Lin","family":"Fu","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University , 22 Qixiangtai Road, Heping District, Tianjin 300070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Du","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University , 22 Qixiangtai Road, Heping District, Tianjin 300070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Furkert","sequence":"additional","affiliation":[{"name":"Leibniz-Forschungsinstitut f\u00fcr Molekulare Pharmakologie , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan L","family":"Shipton","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford , Mansfield Road, Oxford OX1 3QT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University , 22 Qixiangtai Road, Heping District, Tianjin 300070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Leibniz-Forschungsinstitut f\u00fcr Molekulare Pharmakologie , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred C","family":"Chin","sequence":"additional","affiliation":[{"name":"Weill Cornell\/Rockefeller\/Sloan Kettering Tri-Institutional MD-PhD Program , New York, NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M","family":"Riley","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford , Mansfield Road, Oxford OX1 3QT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry V L","family":"Potter","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford , Mansfield Road, Oxford OX1 3QT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Leibniz-Forschungsinstitut f\u00fcr Molekulare Pharmakologie , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University , 22 Qixiangtai Road, Heping District, Tianjin 300070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University , 22 Qixiangtai Road, Heping District, Tianjin 300070 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4300-9948","authenticated-orcid":false,"given":"Chenglai","family":"Fu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University , 22 Qixiangtai Road, Heping District, Tianjin 300070 , China"},{"name":"Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine , 1665 Kongjiang Road, Yangpu District, Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"2024070215274160800_cvae017-B1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s42255-019-0041-z","article-title":"Metabolic messengers: adiponectin","volume":"1","author":"Straub","year":"2019","journal-title":"Nat Metab"},{"key":"2024070215274160800_cvae017-B2","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.cmet.2016.04.011","article-title":"Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk","volume":"23","author":"Stern","year":"2016","journal-title":"Cell Metab"},{"key":"2024070215274160800_cvae017-B3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCRESAHA.120.314458","article-title":"Adiponectin, leptin and cardiovascular disorders","volume":"128","author":"Zhao","year":"2021","journal-title":"Circ 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