↑ Body weight, BMI, obesity (5.0 μg/kg/day); concentric LV remodeling (males); ↑ diastolic BP (females); sex dimorphism: ↑ Ca2+ mobility (males), ↓ (females); changes in SERCA2a, NCX1, PLB, p-PLB, CASQ2; epigenetics: ↑ DNMT3a, sex-specific CpG methylation in CASQ2. The gene discussed is PLN; the disease is obesity due to melanocortin 4 receptor deficiency.