Genetic variants in the FTO gene are robustly associated with increased body mass index (BMI) and obesity risk in humans, primarily by increasing energy intake rather than altering energy expenditure.

The association between FTO SNPs and BMI and the risk of being overweight or obese has been confirmed in multiple populations... The effect of FTO SNPs on BMI is modest, with those individuals homozygous for the risk allele weighing, on average, 3 kg more than those homozygous for the protective allele... data from rodents suggested that Fto might affect neuropeptide Y expression in the hypothalamus, which in turn is known to impact feeding behavior. An investigation of the association between FTO SNPs/expression and neuropeptide levels in human hypothalamus might therefore provide a mechanism for the modulatory effect of FTO SNPs on appetite... Interestingly, data from rodents suggested that Fto might affect neuropeptide Y expression in the hypothalamus, which in turn is known to impact feeding behavior. An investigation of the association between FTO SNPs/expression and neuropeptide levels in human hypothalamus might therefore provide a mechanism for the modulatory effect of FTO SNPs on appetite... Interestingly, data from rodents suggested that Fto might affect neuropeptide Y expression in the hypothalamus, which in turn is known to impact feeding behavior. An investigation of the association between FTO SNPs/expression and neuropeptide levels in human hypothalamus might therefore provide a mechanism for the modulatory effect of FTO SNPs on appetite, although it would be challenging to obtain human hypothalamic material.