SIRT1 and obesity due to melanocortin 4 receptor deficiency: On the other hand, nutrient abundance caused Rpl11-dependent p53 activation, and reduced expression of genes associated with energy metabolism (such as Pgc1α, Ppargc1b, Glut4, and sirtuin 1 (Sirt1)), resulting in reduced NAD+ levels and energy expenditure, ultimately leading to obesity.