SIRT1 and obesity due to melanocortin 4 receptor deficiency: Recent studies have shown that western diet-induced obesity could decrease the expression and activation of AMPKα and SIRT1, intensified aortic oxidative stress, increased related inflammatory responses, and diminished eNOS phosphorylation/activation and NO production, leading to endothelial stiffness, aortic fibrosis, and remodeling [37].