PNPLA2 and obesity due to melanocortin 4 receptor deficiency: For example, whole-body KO of ATGL results in robust cardiac lipid accumulation and a lipotoxic cardiomyopathy phenotype [98], while cardiac-specific ATGL overexpression has been shown to improve in vivo systolic and diastolic function in mice subjected to high-fat/high-sucrose diet-induced obesity [99].