{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:49:55Z","timestamp":1777016995708,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["R2023108"],"award-info":[{"award-number":["R2023108"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["B202303017195"],"award-info":[{"award-number":["B202303017195"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ30795"],"award-info":[{"award-number":["2023JJ30795"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2026JJ80123"],"award-info":[{"award-number":["2026JJ80123"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Membrane\u2010associated RING\u2010CH1 (MARCH1) is a critical membrane\u2010bound RING domain E3 ubiquitin ligase that primarily regulates immune cell development, immune responses, antigen presentation modulation, and metabolic functions. Its role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF) remains elusive. This study aimed to investigate the function of MARCH1 in HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multi\u2010hit (high fat\/sugar diet together with deoxycorticosterone acetate and angiotensin II injection) HFpEF mouse model was established in C57BL\/6 wild\u2010type mice and MARCH1 KO mice. Non\u2010HFpEF control mice received standard diet. Comprehensive evaluation was carried out through echocardiography, histological and biochemical studies. White adipose tissue (WAT) beiging was analyzed in isolated stromal vascular fraction cells. The relevant molecular mechanisms were determined through RNA sequencing and co\u2010immunoprecipitation assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cardiometabolic dysregulation with hypertension and obesity was observed in WT HFpEF mice. Significantly reduced running distance and running time were found in HFpEF mice compared to the WT control mice (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Histologic and echocardiographic examinations also visualized cardiac fibrosis, left ventricular hypertrophy, and diastolic dysfunction in HFpEF mice. MARCH1 expression was significantly upregulated in the WAT of HFpEF mice. MARCH1 deficiency alleviated cardiac dysfunction of HFpEF mice and induced WAT beiging following HFpEF. Mechanistically, MARCH1 contributes to HFpEF by direct binding to Kr\u00fcppel\u2010like factor 15 (KLF15). Overexpressing KLF15 blocked the beiging effects of WAT from MARCH1 KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study highlights the positive anti\u2010fibrotic and WAT beiging effects of MARCH1 inhibition in the setting of HFpEF. Targeting MARCH1 and KLF15 might serve as novel therapeutic options for HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70141","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:46:23Z","timestamp":1776311183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MARCH1<\/scp>\n                    Deletion Attenuates\n                    <scp>HFpEF<\/scp>\n                    by Promoting Adipose Beiging"],"prefix":"10.1002","volume":"16","author":[{"given":"Yunlong","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital of Central South University  Changsha Hunan China"},{"name":"Department of Cardiology The Central Hospital of Xiangtan(The Affiliated Hospital of Hunan University)  Xiangtan Hunan 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