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-following its role as an immune sensor to infection and stress-is 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' 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.

• Klíčová slova
• 3/10 max, IL-33/ST2, adipose tissue, cardiac remodeling, cardiovascular disease, obesity,
• MeSH
• fibróza genetika   metabolismus   MeSH
• ghrelin genetika   metabolismus   MeSH
• interleukin 33 * genetika   metabolismus   MeSH
• interleukin-1 receptor-like 1 protein genetika   metabolismus   MeSH
• kardiomegalie genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   MeSH
• obezita * komplikace   genetika   metabolismus   MeSH
• potkani Zucker MeSH
• receptory interleukinu-1 * genetika   metabolismus   MeSH
• remodelace komor * genetika   fyziologie   MeSH
• výměnné faktory guaninnukleotidů genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ghrelin MeSH
• Il33 protein, rat MeSH Prohlížeč
• interleukin 33 * MeSH
• interleukin-1 receptor-like 1 protein MeSH
• obestatin, rat MeSH Prohlížeč
• Rapgef3 protein, rat MeSH Prohlížeč
• receptory interleukinu-1 * MeSH
• ST2 protein, rat MeSH Prohlížeč
• výměnné faktory guaninnukleotidů MeSH