A recent paper has demonstrated that FTO does not globally target all 6meA-modified mRNAs but instead demethylates specific mRNA subsets172. They show for instance, that the midbrain and striatum of Fto−/− mice show increased methylation in mRNAs from genes encoding components of the dopamine signalling pathway, resulting in reduced dopaminergic signalling tone172. Outside of the brain, FTO risk alleles have also been reported to influence the methylation status of ghrelin mRNA. By doing so, Karra and colleagues have postulated that FTO may affect levels of circulating ghrelin. Further studies will be required to determine the extent to which changes in dopamine and/or ghrelin signalling could be effectors of FTO’s association with increased BMI.173
