Recent studies have highlighted the pivotal role of prolonged ERS-initiated activation of the unfolded protein response (UPR), the ensuing chronic low-grade inflammation, and altered insulin signaling in promoting obesity-compromised cardiovascular system (CVS) (Hotamisligil, 2010; Thorp, 2012; Liu and Dudley, 2014; Szymański et al., 2017; Zhang et al., 2017b). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.