Variation in FTO contributes to childhood obesity and severe adult obesity

Dina, Christian; Meyre, David; Gallina, Sophie; Durand, Emmanuelle; Körner, Antje; Jacobson, Peter; Carlsson, Lena; Kieß, Wieland; Vatin, Vincent; Lecœur, Cécile; Delplanque, Jérôme; Vaillant, Emmanuel; Pattou, François; Ruiz, Jose; Weill, Jacques; Lévy-Marchal, Claire; Horber, Fritz F.; Potoczna, Natascha; Herçberg, Serge; Stunff, Catherine Le; Bougnères, Pierre; Kovacs, Peter; Marre, Michel; Balkau, Beverley; Cauchi, Stéphane; Chèvre, Jean-Claude; Froguel, Philippe

doi:10.1038/ng2048

Cited by 1,428 publications

(1,308 citation statements)

References 11 publications

Supporting

Mentioning

1,159

Contrasting

Unclassified

Order By: Relevance

“…FTO is well recognized for its strong association with increased body mass and obesity 52, 53. Given that obesity is a well‐established risk factor for a wide range of cancers, it is reasonable to postulate that FTO is intimately linked to cancers.…”

Section: The Dual Role Of M6a Modification In Human Cancersmentioning

confidence: 99%

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Wang

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

As the most abundant and reversible RNA modification in eukaryotic cells, m6A triggers a new layer of epi‐transcription. M6A modification occurs through a methylation process modified by “writers” complexes, reversed by “erasers”, and exerts its role depending on various “readers”. Emerging evidence shows that there is a strong association between m6A and human diseases, especially cancers. Herein, we review bi‐aspects of m6A in regulating cancers mediated by the m6A‐associated proteins, which exert vital and specific roles in the development of various cancers. Generally, the m6A modification performs promotion or inhibition functions (dual role) in tumorigenesis and progression of various cancers, which suggests a new concept in cancer regulations. In addition, m6A‐targeted therapies including competitive antagonists of m6A‐associated proteins may provide a new tumour intervention in the future.

show abstract

Section: The Dual Role Of M6a Modification In Human Cancersmentioning

confidence: 99%

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Wang

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…42,43 Recent research is increasingly quantifying the effect of specific genotypes on metabolism or adiposity, with several of these associated with appetite regulation. 3,[44][45][46] Again, these appetite genes may have particular importance for offspring growth rather than adult phenotype. 47 However, the individual effects of these genes are of modest magnitude, hence the genetic basis of variation in adiposity manifests as their composite effect.…”

Section: The Generic Profile Of Thrift In Homo Sapiensmentioning

confidence: 99%

Thrift: a guide to thrifty genes, thrifty phenotypes and thrifty norms

Wells¹

2009

Int J Obes

View full text Add to dashboard Cite

There is a growing interest in evolutionary models of human adiposity. Frequent reference has been made to 'thrifty genes' or 'thrifty phenotypes', referring to a variety of metabolic or behavioural traits that in one or the other way imply frugality in the expenditure or storage of energy. However, there is confusion over how the strategy of thrift has been incorporated into human biology. At the broadest level, humans represent a thrifty species relative to other mammals, indicating that metabolic adaptations had a crucial role in the emergence of the Homo lineage, in particular in buffering reproduction from ecological stochasticity. In contemporary humans, some variability in adiposity may be attributable to genotypes systematically favoured in certain ecological settings. Genetic variability is also present within populations, and may be considered bet hedging (distributing risk across offspring to increase parental fitness). Bet hedging is an alternative to genetic drift for accounting for genetic variability in the absence of strong selective pressures. Contrasting with genetic variability emerging over the long-term, thrifty phenotypes represent a response to short-term ecological variability. Physiological plasticity allows the emergence of variability across the life course in response to ecological cues experienced directly or by very recent ancestors. Finally, cultural norms or individual preferences allow voluntary behavioural manipulation of thrift in individuals. Overall, there is a range of factors and processes both favouring and opposing thrifty genes, which may reflect moderate bet hedging rather than systematic adaptation. Plasticity protects the genome from selective pressures by tailoring the organism to ongoing ecological conditions. The fact that obesity can occur in different individuals through different genotypes, life histories and behaviours indicates that different treatments are also likely to be required.

show abstract

“…Genome‐wide association studies have identified obesity‐associated single nucleotide polymorphisms (SNPs) in a 47kb block of linkage disequilibrium (LD block) at the end of FTO intron 1 (Dina et al ., 2007; Frayling et al, 2007). As a result, FTO was thought to be the causal gene whose function was associated with weight gain (Fawcett and Barroso, 2010).…”

Section: Introductionmentioning

confidence: 99%

BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene

Rinkwitz

Geng

Manning

et al. 2015

Genesis

View full text Add to dashboard Cite

SummarySingle Nucleotide Polymorphisms in FTO intron 1 have been associated with obesity risk, leading to the hypothesis that FTO is the obesity‐related gene. However, other studies have shown that the FTO gene is part of the regulatory domain of the neighboring IRX3 gene and that enhancers in FTO intron 1 regulate IRX3. While Irx3 activity was shown to be necessary in the hypothalamus for the metabolic function of Irx3 in mouse, no enhancers with hypothalamic activity have been demonstrated in the risk‐associated region within FTO. In order to identify potential enhancers at the human FTO locus in vivo, we tested regulatory activity in FTO intron 1 using BAC transgenesis in zebrafish. A minimal gata2 promoter‐GFP cassette was inserted 1.3 kb upstream of the obesity associated SNP rs9939609 in a human FTO BAC plasmid. In addition to the previously identified expression domains in notochord and kidney, human FTO BAC:GFP transgenic zebrafish larvae expressed GFP in the ventral posterior tuberculum, the posterior hypothalamus and the anterior brainstem, which are also expression domains of zebrafish irx3a. In contrast, an in‐frame insertion of a GFP cassette at the FTO start codon resulted in weak ubiquitous GFP expression indicating that the promoter of FTO does likely not react to enhancers located in the obesity risk‐associated region. genesis 53:640–651, 2015. © 2015 The Authors. genesis Published by Wiley Periodicals, Inc.

show abstract

Variation in FTO contributes to childhood obesity and severe adult obesity

Cited by 1,428 publications

References 11 publications

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

The dual role of N6‐methyladenosine modification of RNAs is involved in human cancers

Thrift: a guide to thrifty genes, thrifty phenotypes and thrifty norms

BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene

Contact Info

Product

Resources

About