It has been reported that PVAT mediates the vascular function and remodelling in HFD-induced obesity, which is associated with impaired NOS3-mediated signalling.44 In our A-NOS3 KO mice model, our results coherently demonstrated that the pathology of vascular dysfunction and remodelling was enhanced in the absence of adipocyte NOS3 (Figures 3 and 4), which was associated with augmented expression of oxidative stress markers in the vessel wall. Here, NOS3 is linked to obesity due to melanocortin 4 receptor deficiency.