Document Detail

FTO expression is regulated by availability of essential amino acids.
MedLine Citation:
PMID:  22614055     Owner:  NLM     Status:  MEDLINE    
Genome-wide association studies have revealed that single nucleotide polymorphisms in fat mass and obesity-associated transcript (FTO) are robustly associated with body mass index and obesity. Expression of Fto in the hypothalamic arcuate nucleus is bidirectionally regulated as a function of nutritional status; decreasing following a 48-h fast and increasing after 10-week exposure to a high-fat diet. Here, we utilize an in vitro approach to determine which nutrients could regulate FTO levels at a cellular level. Using mouse and human cell lines, we find that FTO levels are not influenced by serum starvation. We demonstrate, however, that both glucose and total amino-acid deprivation regulates FTO expression. In particular, we have found that FTO mRNA and protein levels are dramatically downregulated by total amino-acid deprivation in mouse hypothalamic N46 cells, mouse embryonic fibroblasts and in human HEK293 cells. The drop rate of Fto mRNA is faster than its rate of natural degradation, pointing to regulation at the transcriptional level, which is reversible upon amino-acid replacement. Strikingly, this downregulation was seen only with essential amino-acid deficiency and not nonessential amino acids. These data suggest that FTO might have a role in the sensing of essential amino-acid availability.
M K Cheung; P Gulati; S O'Rahilly; G S H Yeo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-22
Journal Detail:
Title:  International journal of obesity (2005)     Volume:  37     ISSN:  1476-5497     ISO Abbreviation:  Int J Obes (Lond)     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-07     Completed Date:  2014-02-18     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101256108     Medline TA:  Int J Obes (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  744-7     Citation Subset:  IM    
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MeSH Terms
Amino Acids, Essential / metabolism*
Arcuate Nucleus / metabolism*
Blotting, Western
Cell Line
Diet, High-Fat
Gene Expression Regulation
Genome-Wide Association Study
Glucose / metabolism*
HEK293 Cells
Mixed Function Oxygenases / metabolism*
Obesity / genetics,  metabolism*,  physiopathology
Oxo-Acid-Lyases / metabolism*
Polymorphism, Single Nucleotide
Proteins / metabolism*
RNA, Messenger / metabolism
Time Factors
Grant Support
G0600717//Medical Research Council; G0900554//Medical Research Council; G9824984//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/Amino Acids, Essential; 0/FTO protein, human; 0/Proteins; 0/RNA, Messenger; EC 1.-/Mixed Function Oxygenases; EC 1.14.11.-/FTO protein, mouse; EC 4.1.3.-/Oxo-Acid-Lyases; IY9XDZ35W2/Glucose

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