HFD feeding in A-NOS3 KO mice resulted in (i) an exaggerated blood pressure elevation, (ii) endothelial and PVAT dysfunction that was characterized by the reduced acetylcholine-evoked vascular relaxation and the reduced anti-contractile function of the surrounding PVAT, (iii) vascular remodelling characterized by the elevated vascular smooth muscle proliferation and collagen deposition in the aorta, (iv) elevated inflammation and hypoxia in the aortic PVAT and mPVAT, and (v) the upregulation of chemerin, a novel adipokine involved in metabolic disorders. This evidence concerns the gene RARRES2 and Other metabolic disease.