Abstract 14684: Protective Role of Cardiac Silent Information Regulator 1 Against High Fat Diet-Induced Cardiac Hypertrophy
Background: Obesity and overeating become a common health problem in advanced countries. Obesity is closely correlated to incidence of cardiovascular diseases. Obesity causes lipid accumulation not only in adipose tissue but also in non-adipose tissue. Ectopic lipid accumulation and lipotoxicity induce pancreatic β-cell failure, nonalcoholic steatohepatitis, and cardiomyopathy. Calorie restriction (CR) is known to improve metabolic disorders. We had demonstrated that cardiac Silent information regulator 1 (Sirt1) plays a pivotal role in CR-induced cardioprotection. However, the role of cardiac Sirt1 on high fat diet (HFD)-induced cardiomyopathy remains undetermined.
Methods and Results: Three-month-old male cardiomyocyte-specific Sirt1 knockout mice (CM-Sirt1 KO) and control mice (Cont) were fed a control diet (HFC) or a HFD for 3 months. There were no difference in BW between Cont-HFC and CM-Sirt1 KO-HFC. However, BW increased more in CM-Sirt1 KO-HFD than in Cont-HFD. The expression levels of Sirt1 mRNA did not change with HFD in Cont. [[Unable to Display Character: ②]] Echocardiographic evaluation revealed that there were no difference in LV systolic parameters (%FS and EF) (Figure left), but IVS wall thickness and corrected LV mass in CM-Sirt1KO-HFD were higher than those in Cont-HFD (Figure right). [[Unable to Display Character: ③]] Liver weight increased with HFD in both strains. Hematoxylin-Eosin staining showed a similar degree of steatohepatitis in Cont-HFD and CM-Sirt1 KO-HFD. In contrast, Oil red O staining exhibited massive fat deposition only in CM-Sirt1 KO-HFD and myocardial triglyceride content was significantly higher in CM-Sirt1 KO-HFD.
Conclusions: These results indicate that deficiency in cardiac Sirt1 exacerbates cardiac fat accumulation, indicating that cardiac Sirt1 plays a protective role against HFD-induced cardiomyopathy. Thus, sirtuin-activating compounds have the potential for a novel therapeutic strategy for preventing cardiac lipotoxicity in patients with obesity.
- © 2013 by American Heart Association, Inc.