Therefore, as obesity alone does not elicit HFpEF, the mechanistic underpinnings of obesity-induced cardiomyopathy are different from those in HFpEF, supporting a model in which FoxO1 overactivation in HFpEF leads to the detrimental functional consequences of cardiomyocyte lipid accumulation. This evidence concerns the gene FOXO1 and obesity due to melanocortin 4 receptor deficiency.