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

Area of Science:

• Cardiovascular Biology
• Immunology
• Metabolic Disease

Background:

• Obesity is a major risk factor for cardiovascular disease (CVD) severity and mortality.
• Visceral fat secretes inflammatory adipokines, influencing cardiac metabolism and remodeling.
• Interleukin-33 (IL-33) signaling, via ST2, is implicated in immune responses and cardiac fibrosis.

Purpose of the Study:

• To investigate the effects of IL-33/ST2 signaling on cardiac remodeling in obesity.
• To elucidate molecular pathways linking adipose-derived IL-33 to cardiac fibrosis and hypertrophy.
• To explore the role of ghrelin in modulating IL-33 effects in obesity-related cardiac changes.

Main Methods:

• Utilized the Zucker Fatty rat model of obesity.
• Developed in vitro models to simulate adipose-myocardial interactions.
• Analyzed IL-33/ST2 signaling, Epac proteins, and gene expression in adipose and cardiac tissues.

Main Results:

• Demonstrated dysregulated IL-33/ST2 signaling in adipose and cardiac tissues of obese rats.
• Identified affected Epac proteins and pro-fibrotic gene expression signatures.
• Observed that ghrelin-induced IL-33 secretion counteracted pro-fibrotic effects by influencing transcription factors and ST2 isoform balance.

Conclusions:

• IL-33/ST2 signaling is dysregulated in obesity and contributes to cardiac fibrosis.
• Ghrelin can modulate IL-33 secretion, offering a potential counter-regulatory mechanism.
• The role of IL-33 in cardiac remodeling is complex and context-dependent, influenced by cell origin and ST2 isoform balance.