Role for the obesity-related FTO gene in the cellular sensing of amino acids

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 s...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-02, Vol.110 (7), p.2557-2562
Main Authors: Gulati, Pawan, Cheung, Man Ka, Antrobus, Robin, Church, Chris D., Harding, Heather P., Tung, Yi-Chun Loraine, Rimmington, Debra, Ma, Marcella, Ron, David, Lehner, Paul J., Ashcroft, Frances M., Cox, Roger D., Coll, Anthony P., O'Rahilly, Stephen, Yeo, Giles S. H.
Format: Article
Language:English
Subjects:
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Amino acids
Amino Acids - metabolism
Animals
Antibodies
Biological Sciences
Body Composition - genetics
Body fat
Cell extracts
Cell Fractionation
Chromatography, Liquid
Electrophoresis, Polyacrylamide Gel
Fibroblasts
Food intake
Fractionation
HEK293 Cells
Humans
Immunoprecipitation
Messenger RNA
Mice
Mutation
Obesity
Obesity - genetics
Polymorphism, Single Nucleotide - genetics
Proteins - genetics
Proteins - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Signal Transduction - genetics
Tandem Mass Spectrometry
TOR Serine-Threonine Kinases - metabolism
Transfection
Western blotting
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1222796110