{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T03:07:19Z","timestamp":1782184039553,"version":"3.54.5"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health, Ricerca Corrente","award":["Exceles LX22NPO5104"],"award-info":[{"award-number":["Exceles LX22NPO5104"]}]},{"name":"Italian Ministry of Health, Ricerca Corrente","award":["MH CZ DRO VFN 64165"],"award-info":[{"award-number":["MH CZ DRO VFN 64165"]}]},{"name":"Ministry of Education, Youth and Sport of the Czech Republic","award":["Exceles LX22NPO5104"],"award-info":[{"award-number":["Exceles LX22NPO5104"]}]},{"name":"Ministry of Education, Youth and Sport of the Czech Republic","award":["MH CZ DRO VFN 64165"],"award-info":[{"award-number":["MH CZ DRO VFN 64165"]}]},{"name":"Czech Ministry of Health","award":["Exceles LX22NPO5104"],"award-info":[{"award-number":["Exceles LX22NPO5104"]}]},{"name":"Czech Ministry of Health","award":["MH CZ DRO VFN 64165"],"award-info":[{"award-number":["MH CZ DRO VFN 64165"]}]},{"name":"Cooperatio Medical Diagnostics","award":["Exceles LX22NPO5104"],"award-info":[{"award-number":["Exceles LX22NPO5104"]}]},{"name":"Cooperatio Medical Diagnostics","award":["MH CZ DRO VFN 64165"],"award-info":[{"award-number":["MH CZ DRO VFN 64165"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is an epidemic condition linked to cardiovascular disease severity and mortality. Fat localization and type represent cardiovascular risk estimators. Importantly, visceral fat secretes adipokines known to promote low-grade inflammation that, in turn, modulate its secretome and cardiac metabolism. In this regard, IL-33 regulates the functions of various immune cells through ST2 binding and\u2014following its role as an immune sensor to infection and stress\u2014is involved in the pro-fibrotic remodeling of the myocardium. Here we further investigated the IL-33\/ST2 effects on cardiac remodeling in obesity, focusing on molecular pathways linking adipose-derived IL-33 to the development of fibrosis or hypertrophy. We analyzed the Zucker Fatty rat model, and we developed in vitro models to mimic the adipose and myocardial relationship. We demonstrated a dysregulation of IL-33\/ST2 signaling in both adipose and cardiac tissue, where they affected Epac proteins and myocardial gene expression, linked to pro-fibrotic signatures. In Zucker rats, pro-fibrotic effects were counteracted by ghrelin-induced IL-33 secretion, whose release influenced transcription factor expression and ST2 isoforms balance regulation. Finally, the effect of IL-33 signaling is dependent on several factors, such as cell types\u2019 origin and the balancing of ST2 isoforms. Noteworthy, it is reasonable to state that considering IL-33 to have a unique protective role should be considered over-simplistic.<\/jats:p>","DOI":"10.3390\/ijms24031991","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:22:10Z","timestamp":1674109330000},"page":"1991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Unveiling IL-33\/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-7597","authenticated-orcid":false,"given":"Clementina","family":"Sitzia","sequence":"first","affiliation":[{"name":"Department of Biomedical Science for Health, Medical Faculty, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vianello","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science for Health, Medical Faculty, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5833-0780","authenticated-orcid":false,"given":"Elena","family":"Dozio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science for Health, Medical Faculty, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5928-3074","authenticated-orcid":false,"given":"Marta","family":"Kalousov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostic, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Zima","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Laboratory Diagnostic, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12108 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-5774","authenticated-orcid":false,"given":"Stefano","family":"Brizzola","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Science, University of Milan, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-4612","authenticated-orcid":false,"given":"Paola","family":"Roccabianca","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Science, University of Milan, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"CRC \u201cInnovation for Well-Being and Environment\u201d (I-WE), University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lamont","sequence":"additional","affiliation":[{"name":"R&D, RANDOX Laboratories Ltd., County Antrim BT29 4QY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Tacchini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science for Health, Medical Faculty, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7928-7697","authenticated-orcid":false,"given":"Massimiliano Marco","family":"Corsi-Romanelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science for Health, Medical Faculty, University of Milan, 20122 Milan, Italy"},{"name":"U.O.C. SMEL-1 of Clinical Pathology, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11883-016-0575-4","article-title":"Obesity and Cardiovascular Disease: A Risk Factor or a Risk Marker?","volume":"18","author":"Mandviwala","year":"2016","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E384","DOI":"10.1152\/ajpendo.90975.2008","article-title":"Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action","volume":"297","author":"Wang","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. 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