High-Fat Diet Augments Myocardial Inflammation and Cardiac Dysfunction in Arrhythmogenic Cardiomyopathy

Area of Science:

• Cardiology
• Genetics
• Nutrition Science

Background:

• Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease causing dysfunction, arrhythmias, and inflammation.
• Environmental factors like diet may influence ACM progression, but their specific impact remains under investigation.

Purpose of the Study:

• To investigate the impact of a high-fat diet (HFD) on the pathogenesis and progression of arrhythmogenic cardiomyopathy (ACM).

Main Methods:

• A robust ACM mouse model (Desmoglein-2 mutant, Dsg2mut/mut) was fed either an HFD or control chow for 8 weeks.
• Echocardiography, electrocardiography, and assessments of lipid burden, inflammatory markers, and fibrosis were performed.

Main Results:

• HFD-fed Dsg2mut/mut mice exhibited worsened cardiac dysfunction, including arrhythmias, left ventricle remodeling, and reduced ejection fraction (%LVEF).
• Elevated plasma high-density lipoprotein (HDL) correlated with %LVEF, and myocardial adipokines (AdipoQ, FGF1) were increased, without increased cardiac fibrosis.
• The HFD exacerbated certain ACM phenotypes but did not worsen all aspects of the disease.

Conclusions:

• Diet, specifically a high-fat diet, can significantly impact ACM progression, worsening cardiac dysfunction and remodeling.
• Elevated AdipoQ and HDL's positive correlation with %LVEF suggest potential protective mechanisms warranting further study.
• Dietary modification represents a potential therapeutic avenue for managing arrhythmogenic cardiomyopathy.