FTO and obesity due to melanocortin 4 receptor deficiency: For example, H3K27me3 deposited by EZH2 suppresses the transcription of genes encoding negative regulators of mTORC1 such as TSC2 and DEPTOR, rendering enhanced mTORC1 activity to attenuate autophagy (Wei et al., 2015); and intriguingly, the fat mass and obesity-associated protein (FTO) catalyzes m6A demethylation in a Fe (II)- and α-KG-dependent manner (Jia et al., 2011), and depletion of FTO in mouse embryonic fibroblasts can weaken the activation of the mTORC1 pathway, leading to enhanced autophagy (Gulati et al., 2013).