FTO - A Gene Contributing to Human Obesity

FTO is a very large gene, also known as fat mass and obesity associated gene.

FTO (Fat mass and obesity-associated protein) mRNA is widely expressed in different tissues, especially in the brain, but also in skeletal muscles and adipose tissue. In the mice brain, Fto is highly expressed in hypothalamic nuclei that control eating behavior.

The protein is an dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. It has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. FTO has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. It has no activity towards 1-methylguanine. There is no detectable activity towards double-stranded DNA. The enzyme requires molecular oxygen, alpha-ketoglutarate and iron.

FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis as well as to the regulation of body size and body fat accumulation (www.uniprot.org).