Obesity represents a major non-cardiac comorbidity of HFpEF and obesity-related HFpEF constitutes a distinct clinical phenotype [9,10] with a particular biomarker profile characterized by overproduction of adipocyte-derived signaling molecules such as leptin and neprilysin, and the consequences thereof (i.e., hypervolemia and lower levels of natriuretic peptides) [11]. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.