1. Role for the obesity-related FTO gene in the cellular sensing of amino acids
- Author
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Debra Rimmington, Yi-Chun Loraine Tung, Roger D. Cox, Man Ka Cheung, Heather P. Harding, Pawan Gulati, Anthony P. Coll, Paul J. Lehner, Marcella Ma, Frances M. Ashcroft, David Ron, Giles S.H. Yeo, Chris Church, Stephen O'Rahilly, and Robin Antrobus
- Subjects
endocrine system diseases ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,mTORC1 ,Nutrient sensing ,Biology ,Cell Fractionation ,FTO gene ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Tandem Mass Spectrometry ,Animals ,Humans ,Immunoprecipitation ,Obesity ,Amino Acids ,Loss function ,030304 developmental biology ,Genetics ,chemistry.chemical_classification ,0303 health sciences ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,TOR Serine-Threonine Kinases ,HEK 293 cells ,Intron ,Proteins ,nutritional and metabolic diseases ,pathological conditions, signs and symptoms ,Fibroblasts ,Biological Sciences ,Amino acid ,HEK293 Cells ,chemistry ,030220 oncology & carcinogenesis ,Body Composition ,Electrophoresis, Polyacrylamide Gel ,Chromatography, Liquid ,Signal Transduction - Abstract
SNPs in the first intron of FTO ( fat mass and obesity associated ) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in severe growth retardation, and mice globally overexpressing FTO are obese. The mechanisms through which FTO influences growth and body composition are unknown. We describe a role for FTO in the coupling of amino acid levels to mammalian target of rapamycin complex 1 signaling. These findings suggest that FTO may influence body composition through playing a role in cellular nutrient sensing.
- Published
- 2013