Key result
Ghrelin counteracts obesity-induced cardiac fibrosis by restoring IL-33/ST2 signaling in preclinical models.
Why the study?
To investigate 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.
Does obesity alter the IL-33/ST2 pathway and promote cardiac remodeling in a rat model?
Does obesity alter the IL-33/ST2 pathway and promote cardiac remodeling in a rat model?
The IL-33/ST2 pathway is dysregulated in obesity, promoting pro-fibrotic cardiac remodeling that may be counteracted by ghrelin, suggesting that viewing IL-33 as solely cardioprotective is over-simplistic.
Challenges simplistic view of IL-33 as cardioprotective in obesity; hypothesis-generating for ghrelin in human cardiac fibrosis.
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.
No takes yet. Share an insight, caveat, or question.
Sitzia et al. (2023) studied Obesity-induced cardiac remodeling (n=20). Obesity (fa/fa- mutation) vs. Lean littermates was evaluated on Cardiac IL-33/ST2 signaling and pro-fibrotic remodeling markers. Obesity in Zucker rats caused a dysregulation of the IL-33/ST2 axis and reduced Epac1 expression, leading to pro-fibrotic signaling that was counteracted by ghrelin-induced IL-33 secretion.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: