FTO and ALKBH5 primarily demethylate m6A- modified bases, with FTO being the first m6A demethylase identified, showing high demethylation activity for m6A, and ALKBH5 catalyzing the removal of m6A modifications from nuclear RNAs (mainly mRNA), thereby affecting metabolic disease and human obesity. Here, FTO is linked to obesity due to melanocortin 4 receptor deficiency.