MYCN and Obesity: This compound increased mitochondrial respiration, causing upregulation of the NAD+/NADH and α-KG/2-hydroxyglutarate (2-HG) ratio, which in turn resulted in promoter CpG island demethylation, activating the differentiation program in MYCN-amplified NB.135 In addition, we previously showed that inhibition of fatty acid synthase (FASN) or acetyl-CoA carboxylase A (ACACA) with TOFA, Cerulenin, Orlistat (approved for treatment of obesity), Soraphen A, or UB006 (Figure 3), induced NB differentiation independently of MYCN status.101