title: The biology of FTO: from nucleic acid demethylase to amino acid sensor.
abstract: Genome-wide association studies have revealed that single-nucleotide polymorphisms in the first intron of the gene encoding fat mass and obesity-associated protein (FTO) are robustly associated with BMI and obesity. Subsequently, this association with body weight, which is replicable across multiple populations and different age groups, has been unequivocally linked to increased food intake. Although evidence from a number of animal models with perturbed FTO expression indicates a role for FTO in energy homeostasis, to date, no conclusive link has been made between the risk alleles and FTO expression or its physiological role. FTO is a nucleic acid demethylase, and a deficiency in FTO leads to a complex phenotype highlighted by postnatal growth retardation, pointing to some fundamental developmental role. Recent emerging data now points to a role for FTO in the sensing of nutrients and the regulation of translation and growth. In this review, we explore the in vivo and in vitro evidence detailing the complex biology of FTO and discuss how these might link to the regulation of body weight.
authors.affiliation: MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Box 289, Cambridge CB2 0QQ, UK.
authors.forename: Pawan
authors.initials: P
authors.lastname: Gulati
authors.forename: Giles S H
authors.initials: GS
authors.lastname: Yeo
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D004435:Eating / Q000235:genetics / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
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