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PMID: 24627050 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

FTO and obesity: mechanisms of association.

Current diabetes reports ·Vol. 14 ·No. 5 ·2014-00-00 ·Pages 486

Zhao X, Yang Y, Sun BF, Zhao YL, Yang YG

Abstract

The Fat mass and obesity associated (FTO) gene is a newly identified genetic factor for obesity. However, the exact molecular mechanisms responsible for the effect of FTO on obesity remain largely unknown. Recent studies from genome-wide associated studies reveal that genetic variants in the FTO gene are associated not only with human adiposity and metabolic disorders, but also with cancer, a highly obesity-associated disease as well. Data from animal and cellular models further demonstrate that the perturbation of FTO enzymatic activity dysregulates genes related to energy metabolism, causing the malfunction of energy and adipose tissue homeostasis in mice. The most significant advance about FTO research is the recent discovery of FTO as the first N6-methyl-adenosine (m(6)A) RNA demethylase that catalyzes the m(6)A demethylation in α-ketoglutarate - and Fe(2+)-dependent manners. This finding provides the strong evidence that the dynamic and reversible chemical m(6)A modification on RNA may act as a novel epitranscriptomic marker. Furthermore, the FTO protein was observed to be partially localized onto nuclear speckles enriching mRNA processing factors, implying a potential role of FTO in regulating RNA processing. This review summarizes the recent progress about biological functions of FTO through disease-association studies as well as the data from in vitro and in vivo models, and highlights the biochemical features of FTO that might be linked to obesity.

MeSH Terms
Adipose Tissue Alpha-Ketoglutarate-Dependent Dioxygenase FTO Animals Epigenesis, Genetic Female Genetic Variation Genome-Wide Association Study Humans Male Metabolic Diseases/genetics,physiopathology Mice Mixed Function Oxygenases/genetics Neoplasms/genetics,physiopathology Obesity/genetics,physiopathology Oxo-Acid-Lyases/genetics Polymorphism, Single Nucleotide Proteins/genetics RNA, Messenger
Chemicals
Proteins RNA, Messenger Mixed Function Oxygenases FTO protein, mouse Alpha-Ketoglutarate-Dependent Dioxygenase FTO FTO protein, human Oxo-Acid-Lyases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhao Xu
Laboratory of Genome Variations and Precision Biomedicine, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1-7 Beichen West Road, Chaoyang District, Beijing, 100101, China.
Yang Ying
Sun Bao-Fa
Zhao Yong-Liang
Yang Yun-Gui
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Article Info
Journal
Current diabetes reports
Abbr.
Curr Diab Rep
ISSN
1539-0829
DOI
10.1007/s11892-014-0486-0
Published
2014-00-00
Pages
486
Language
English
Region
United States
NLM ID
101093791
Subset
IM
External Links
PubMed source DOI: 10.1007/s11892-014-0486-0 View journal details
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