Recent work4,17 has demonstrated that FTO codes for a protein expressed in the hypothalamus, the function of which is impacted in many obesity-related genetic defects in humans. Because FTO is down-regulated by Krebs cycle intermediates,4 it is conceivable that this protein is involved in incompletely understood nutrient sensing pathways, which are pivotal to central regulation of energy intake. Thus, a mechanism whereby increased physical activity can negate the association of FTO variants with fat accretion could be through pertubation of energy flux resulting in alterations in expression of FTO.
