For instance, we recently demonstrated that lymphatic valve deficiency results from diet-induced obesity in WT mice; and diet-induced obese ApoE-KO mice display an even more severe dysfunctional phenotype including hyperpermeability and contractile impairment, in addition to profound valve dysfunction (Castorena-Gonzalez, 2022; Davis et al., 2022b). Here, APOE is linked to obesity due to melanocortin 4 receptor deficiency.