Indeed, down-regulation of CPS1 results in the accumulation of uric acid [65], which may activate mitogen-activated protein kinase (MAPK) signaling pathway [66], and also cause inflammation, oxidative stress, insulin resistance, and metabolic syndrome, during the progression of liver disease [67], obesity, and T2DM [68]. This evidence concerns the gene WNK2 and obesity due to melanocortin 4 receptor deficiency.