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Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats

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 metabo...

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Autores principales: Sitzia, Clementina, Vianello, Elena, Dozio, Elena, Kalousová, Marta, Zima, Tomáš, Brizzola, Stefano, Roccabianca, Paola, Tedeschi, Gabriella, Lamont, John, Tacchini, Lorenza, Corsi-Romanelli, Massimiliano Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916239/
https://www.ncbi.nlm.nih.gov/pubmed/36768322
http://dx.doi.org/10.3390/ijms24031991
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author Sitzia, Clementina
Vianello, Elena
Dozio, Elena
Kalousová, Marta
Zima, Tomáš
Brizzola, Stefano
Roccabianca, Paola
Tedeschi, Gabriella
Lamont, John
Tacchini, Lorenza
Corsi-Romanelli, Massimiliano Marco
author_facet Sitzia, Clementina
Vianello, Elena
Dozio, Elena
Kalousová, Marta
Zima, Tomáš
Brizzola, Stefano
Roccabianca, Paola
Tedeschi, Gabriella
Lamont, John
Tacchini, Lorenza
Corsi-Romanelli, Massimiliano Marco
author_sort Sitzia, Clementina
collection PubMed
description 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.
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spelling pubmed-99162392023-02-11 Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats Sitzia, Clementina Vianello, Elena Dozio, Elena Kalousová, Marta Zima, Tomáš Brizzola, Stefano Roccabianca, Paola Tedeschi, Gabriella Lamont, John Tacchini, Lorenza Corsi-Romanelli, Massimiliano Marco Int J Mol Sci Article 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. MDPI 2023-01-19 /pmc/articles/PMC9916239/ /pubmed/36768322 http://dx.doi.org/10.3390/ijms24031991 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sitzia, Clementina
Vianello, Elena
Dozio, Elena
Kalousová, Marta
Zima, Tomáš
Brizzola, Stefano
Roccabianca, Paola
Tedeschi, Gabriella
Lamont, John
Tacchini, Lorenza
Corsi-Romanelli, Massimiliano Marco
Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
title Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
title_full Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
title_fullStr Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
title_full_unstemmed Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
title_short Unveiling IL-33/ST2 Pathway Unbalance in Cardiac Remodeling Due to Obesity in Zucker Fatty Rats
title_sort unveiling il-33/st2 pathway unbalance in cardiac remodeling due to obesity in zucker fatty rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916239/
https://www.ncbi.nlm.nih.gov/pubmed/36768322
http://dx.doi.org/10.3390/ijms24031991
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