LEP and obesity due to melanocortin 4 receptor deficiency: A lack of leptin signaling or leptin resistance increases the risk of cardiac dysfunction and HF, which is a major contributor to morbidity and mortality associated with obesity and type 2 diabetes.76 Activation of the leptin–aldosterone– neprilysin axis appears to play a significant role in the development and progression of HF in obese individuals, regardless of its phenotype.