Thus, a cell without FTO is one that thinks it is starving of amino acids, reducing mTORC1 signaling and increasing autophagy in an effort to ensure cellular survival by maintaining cellular energy levels. The consequence of this in a whole organism is clearly illustrated in another recent study, when a targeted deletion of Fto in adult mice results in a loss of body weight, with all of the change in weight down to a dramatic loss in lean mass.158 As skeletal muscle is the largest depot of protein in the body, it appears to be the most sensitive to the sudden removal of FTO and subsequent increase in autophagy. In contrast, when FTO is postnatally deleted specifically from the mediobasal hypothalamus, there is a more subtle weight loss, resulting from a change in food intake.158
