Endocrine Abstracts

Aims/hypothesis: Obesity and diabetes enhance the risk of developing cardiovascular diseases and heart failure. These metabolic disorders are generally reflected by natriuretic peptides system deficiency. Since brain natriuretic peptide (BNP) is known to influence metabolism and cardioprotection, we investigated the effect of chronic exogenous BNP treatment on adverse myocardial consequences related to obesity and diabetes.

Methods: Ten-week-old C57BL/KsJ-db/db obese diabetic mice (db/db) and their lean control littermates (db/+) were treated with BNP (0.6 μg/kg per h) or saline during 12 weeks (n=10/group). Serial blood and tomography analysis were performed. Cardiac function was determined by echocardiography, and biochemical and histological heart and fat analysis were also performed.

Results: BNP treatment resulted in an average increase in plasma levels of 70 pg/ml. An improvement in the metabolic profile of db/db mice was observed, including a reduction in fat content, increased insulin sensitivity, improved glucose tolerance and lower blood glucose, despite increase food intake. Db/db mice receiving saline displayed both early systolic and diastolic dysfunction whereas these functional changes were prevented by BNP treatment. The cardioprotective effects of BNP were attributed to the inhibition of cardiomyocytes apoptosis, myocardial fibrosis, cardiac hypertrophy and advanced glycation end-products/ receptor for advanced glycation end-products (AGE/RAGE) as well as normalization of cardiac 5′ adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) activities.

Conclusion/interpretation: This study demonstrated beneficial effect of chronic low dose infusion of BNP on metabolism profile together with the prevention of diabetic heart disease in db/db mice model. Cardioprotective mechanisms of BNP include normalization of cardiac AMPK and eNOS activities as well as a reduced cardiac AGE formation. These observations clearly suggest a potential role for BNP in replacement therapy for the prevention of cardiovascular complications of diabetes and obesity.