Recent reports suggest that this strain exhibits a weaker HFpEF phenotype in the two-hit model, including limited diastolic dysfunction.18 While our two-hit HFpEF model shows the phenotypic requirements of obesity, glucose metabolism abnormalities, cardiac remodelling (hypertrophy and fibrosis) and dysfunction (declined GLS), it cannot be ruled out that this may impact our study's objective of confirming the long-term effects of VHL deletion in cardiomyocytes. This evidence concerns the gene VHL and obesity due to melanocortin 4 receptor deficiency.