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 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.
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. pg367@cam.ac.uk
Pawan
P
Gulati
Man Ka
MK
Cheung
Robin
R
Antrobus
Chris D
CD
Church
Heather P
HP
Harding
Yi-Chun Loraine
YC
Tung
Debra
D
Rimmington
Marcella
M
Ma
David
D
Ron
Paul J
PJ
Lehner
Frances M
FM
Ashcroft
Roger D
RD
Cox
Anthony P
AP
Coll
Stephen
S
O'Rahilly
Giles S H
GS
Yeo
D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000235:genetics*; D002458:Cell Fractionation; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D000596:Amino Acids; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases