{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T18:09:31Z","timestamp":1779127771846,"version":"3.51.4"},"reference-count":31,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL 136951,HL 154001"],"award-info":[{"award-number":["HL 136951,HL 154001"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIA","award":["AG07942"],"award-info":[{"award-number":["AG07942"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,9]]},"abstract":"<jats:p>Regulation of organismal homeostasis in response to nutrient availability is a vital physiological process that involves interorgan communication. The role of the heart in controlling systemic metabolic health is not clear. Adopting a mouse model of diet-induced obesity, we found that the landscape of N6-methyladenosine (m6A) on cardiac mRNA was altered following high-fat\/high-carbohydrate feeding (Western diet). m6A is a critical posttranscriptional regulator of gene expression, the formation of which is catalyzed by methyltransferase-like 3 (METTL3). Through parallel unbiased approaches of Nanopore sequencing, mass spectrometry, and protein array, we found regulation of circulating factors under the control of METTL3. Mice with cardiomyocyte-specific deletion of METTL3 showed a systemic inability to respond to nutritional challenge, thereby mitigating the detrimental effects of Western diet. Conversely, increasing cardiac METTL3 level exacerbated diet-induced body weight gain, adiposity, and glucose intolerance. Our findings position the heart at the center of systemic metabolism regulation and highlight an m6A-dependent pathway to be exploited for the battle against obesity.<\/jats:p>","DOI":"10.1172\/jci.insight.188414","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T12:00:21Z","timestamp":1745496021000},"source":"Crossref","is-referenced-by-count":2,"title":["The cardiac METTL3\/m6A pathway regulates the systemic response to Western diet"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-8706","authenticated-orcid":true,"given":"Charles","family":"Rabolli","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, Dorothy M. 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