In addition, cells lacking FTO display decreased activation of the mTORC1 pathway and increased autophagy, all of which makes mechanistic sense in explaining the growth retardation phenotype seen in Fto−/− mice157 and in humans homozygous for loss-of-function FTO mutations.159 The dramatic regulation of FTO by AAs165 seems to be necessary for the cellular response to changing AA levels, as expression of exogenous FTO in cells renders them insensitive to AA deprivation by preventing the expected reduction in mTORC1 signaling.166
