Abstract 11582: Angiotensin 1-7 Ameliorates Diabetic Cardiomyopathy in db/db Mice by Reducing Lipotoxicity: A Critical Role for Adipose Triglyceride Lipase
Background and Aims: Diabetic cardiomyopathy is one of the leading causes of morbidity and mortality in diabetic patients and is commonly associated with obesity. Angiotensin 1-7 (Ang 1-7), a new component of the renin-angiotensin system, can have beneficial effects on energy metabolism. However, the effects of Ang 1-7 on diabetic cardiomyopathy and the potential mechanism involved are incompletely understood. We, therefore, studied the effects of Ang 1-7 on diabetic cardiomyopathy in db/db mice.
Methods and Results: Ang 1-7 was administered to 5-month-old male db/db mice for 1 month via implanted osmotic minipumps. Echocardiography showed Ang 1-7 treatment ameliorated concentric hypertrophy and diastolic dysfunction with preserved systolic function in db/db mice. The functional improvement by Ang 1-7 treatment was accompanied by reduction in systemic fat mass and improvement of the plasma lipid profile. Cardiac energy metabolic changes were measured in isolated working hearts perfused with 5 mM [U-14C] glucose, 1.2 mM [9, 10-3H] palmitate, 3% bovine serum albumin, and 2.5 mM Ca2+, in the presence or absence of insulin (100μU/mL). Ang 1-7 treatment significantly improved glucose oxidation without affecting palmitate oxidation in db/db mice. Histological analysis showed that Ang 1-7 treatment improved cardiac fibrosis and lipotoxicity in db/db mice, concomitantly with a decrease in cardiac triacylglycerol and ceramide levels. Western blotting analysis showed that Ang 1-7 treatment enhanced ATGL expression in db/db mice, which may have occurred due to a deacetylation of FOXO1 via SIRT1.
Conclusions: This study shows that Ang 1-7 has beneficial effects on diabetic cardiomyopathy due to reduced adipose tissue burden and an improvement in lipotoxicity. Angiotensin 1-7 represents a potential new therapy for obesity and/or diabetic cardiomyopathy.
- © 2013 by American Heart Association, Inc.