The study investigates the role of the *FTO* gene, which is associated with increased body mass index in humans, in nucleic acid demethylation. Bioinformatics analysis reveals that FTO shares sequence motifs with Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenases. Recombinant murine Fto is shown to catalyze the Fe(II)- and 2OG-dependent demethylation of 3-methylthymine in single-stranded DNA, producing succinate, formaldehyde, and carbon dioxide. Fto localizes to the nucleus in transfected cells, suggesting a potential role in nucleic acid demethylation. Wild-type mice studies indicate that *Fto* mRNA is most abundant in the brain, particularly in hypothalamic nuclei controlling energy balance, and that *Fto* mRNA levels in the arcuate nucleus are regulated by feeding and fasting. The study suggests that altered FTO demethylase activity may underlie the enhanced fat mass associated with FTO gene variants, potentially through changes in food intake or energy expenditure. Further research is needed to determine the physiologically relevant substrate of FTO and its impact on obesity.The study investigates the role of the *FTO* gene, which is associated with increased body mass index in humans, in nucleic acid demethylation. Bioinformatics analysis reveals that FTO shares sequence motifs with Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenases. Recombinant murine Fto is shown to catalyze the Fe(II)- and 2OG-dependent demethylation of 3-methylthymine in single-stranded DNA, producing succinate, formaldehyde, and carbon dioxide. Fto localizes to the nucleus in transfected cells, suggesting a potential role in nucleic acid demethylation. Wild-type mice studies indicate that *Fto* mRNA is most abundant in the brain, particularly in hypothalamic nuclei controlling energy balance, and that *Fto* mRNA levels in the arcuate nucleus are regulated by feeding and fasting. The study suggests that altered FTO demethylase activity may underlie the enhanced fat mass associated with FTO gene variants, potentially through changes in food intake or energy expenditure. Further research is needed to determine the physiologically relevant substrate of FTO and its impact on obesity.