Given the evidence above that FTO is nutritionally regulated and can influence food intake, could FTO be acting as a nutrient sensor? Initial attention focused on 2-OG, a key intermediate in the citric-acid cycle, and a co-substrate of FTO. It was plausible that FTO could function as a sensor for intracellular concentrations of this metabolite and thus cellular metabolism. However, since typical intracellular concentrations of 2-OG are more than 10-fold higher than its calculated Km of 2.88μM, it is unlikely that FTO’s physiological role is to sense 2-OG, even if it is required as a co-factor for FTO activity.164
