Our results demonstrate that ablation of cardiomyocyte-derived BDNF during the development stage does not impair survival, growth or reproduction; however, in the young adult heart, it causes cardiomyocyte death, degeneration of the myocardium, cardiomyocyte hypertrophy, decreased cardiac function, increased cardiac inflammation and ROS activity, and metabolic disorders, leading to HF in the adult heart and eventually resulting in a decrease in the one-year survival rate. Here, BDNF is linked to metabolic disease.