Abstract 17970: Cardiac Specific Overexpression of Histone Deacetylase 4 Aggravates High Fat Diet-Induced Cardiac Dysfunction and Metabolic Disorders
Introduction: Histone deacetylase are recently identified as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of this specific HDAC isoform in the heart controlling cardiac and systemic disturbances in diabetes and obesity remains unknown.
Hypothesis: This study sought to determine whether cardiac-specific overexpression of HDAC4 could modulate cardiac dysfunction and metabolic disturbance in high fat diet-induced diabetes and obesity.
Methods: Adult wild type mice and cardiac-specific HDAC4 overexpression mice were fed with either a high-fat diet (HFD) or standard chow diet for 16 weeks, respectively. Cardiac function was monitored by using echocardiography. Metabolic features, glucose tolerance, insulin tolerance, and remodeling were determined. Histological analyses were performed to evaluate lipid accumulation in liver, skeletal muscle and adipose tissue.
Results: As compared to chow fed group, HFD-fed mice demonstrated myocardial dysfunction, profound interstitial fibrosis, and cardiac hypertrophy, which further exacerbated in cardiac-HDAC4 transgenic mice. Notably, HFD-induced metabolic syndrome features insulin resistance, obesity, hyperinsulinemia, hyperglycemia, lipid accumulations in liver and skeletal muscle, which were further disturbed in cardiac-HDAC4 transgenic mice.
Conclusion: The results indicated that cardiac specific HDAC4 overexpression enhanced cardiac dysfunction and systemic metabolic disorder in diabetes and obesity.
Author Disclosures: J. Du: None. L. Zhang: None. H. Wang: None. Y.T. Zhao: None. N. Yano: None. T.C. Zhao: None.
- © 2016 by American Heart Association, Inc.