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The fat mass and obesity-associated (FTO) gene: Obesity and beyond?
Martin E Hess1, Jens C Brüning1
1Max Planck Institute for Neurological Research, D-50931 Cologne, Germany; Department of Mouse Genetics and Metabolism, Institute for Genetics, Center of Molecular Medicine Cologne (CMMC), D-50674 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), D-50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital of Cologne, D-50931 Cologne, Germany.
Abstract:
Genome wide association studies undoubtedly linked variants of the fat mass and obesity-associated protein (FTO) to obesity. To date, however, knowledge on the mechanisms coupling variants in the intron of the FTO gene to its expression or enzymatic activity to alter metabolism remains scarce. Until recently, the investigation of the molecular function of FTO had not led to conclusive results concerning the 'where', 'when' and 'how' of FTO activity. Finally, since FTO was identified as a RNA modifying enzyme, demethylating N6-methyladenosine on single stranded RNA, novel understanding of the molecular function is gathered. These and other studies suggest the requirement for a further reaching approach to further investigate FTO function, since the phenotype of aberrant FTO function may encompass more than just obesity. Taking these new insights and translating them into appropriate paradigms for functional research in humans may lead to a deeper understanding of the human physiology and disease. This article is part of a Special Issue entitled: From Genome to Function.
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