It has been reported that increasing levels of leptin in diet-induced obesity (DIO) mice drives an increase in blood pressure and re-expression of LEPR in DIO LEPR-deficient mice also lead to an increase in blood pressure, while humans with loss-of-function mutations in leptin and LEPR have low blood pressure [39]. This evidence concerns the gene LEPR and obesity due to melanocortin 4 receptor deficiency.