Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study.
Ron Do,Swneke D. Bailey,Katia Desbiens,Alexandre Belisle,Alexandre Montpetit,Claude Bouchard,Louis Pérusse,Marie-Claude Vohl,James C. Engert +8 more
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TLDR
It is confirmed that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels, as well as several obesity-related phenotypes.Abstract:
Objective: A genome-wide association study conducted by the Welcome Trust Case Control Consortium recently associated SNPs in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity. Other research groups found similar results in Europeans and Hispanics, but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in obesity, insulin sensitivity and body-weight regulation, including energy intake and expenditure. Research Design and Methods: We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study (QFS), a long-term study of extensively phenotyped individuals that was designed to investigate factors involved in adiposity. Results: We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated with BMI (p=0.0014), weight (p=0.0059) and waist circumference (p=0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin (p=0.011), HOMA-IR (p=0.038) and an insulin sensitivity index derived from an oral glucose tolerance test (p=0.0091). Associations were also found with resting metabolic rate (p=0.042) and plasma leptin levels (p=0.036). Adjustment for BMI abolished the associations with insulin sensitivity, resting metabolic rate and plasma leptin levels. Conclusion: These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, and thus to insulin resistance and increased plasma leptin levels.read more
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N6-methyladenosine Modulates Messenger RNA Translation Efficiency
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Overexpression of Fto leads to increased food intake and results in obesity.
Chris Church,Lee Moir,Fiona McMurray,Christophe Girard,Gareth Banks,Lydia Teboul,Sara Wells,Jens C. Brüning,Patrick M. Nolan,Frances M. Ashcroft,Roger D. Cox +10 more
TL;DR: This study provides the first direct evidence that increased Fto expression causes obesity in mice and shows here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or a high-fat diet.
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Obesity Associated Genetic Variation in FTO Is Associated with Diminished Satiety
Jane Wardle,Susan Carnell,Claire M. A. Haworth,I. Sadaf Farooqi,Stephen O'Rahilly,Robert Plomin +5 more
TL;DR: It is concluded that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite and the relationship between a validated measure of children's habitual appetitive behavior and FTO obesity risk genotype is examined.
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ALKBH1-Mediated tRNA Demethylation Regulates Translation.
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TL;DR: This work shows that mammalian ALKBH1 is a tRNA demethylase that mediates the demethylation of N1-methyladenosine in tRNAs and uncover reversible methylation of tRNA as a new mechanism of post-transcriptional gene expression regulation.
Journal ArticleDOI
Polymorphisms of the FTO Gene Are Associated With Variation in Energy Intake, but not Energy Expenditure
TL;DR: The FTO genotype was significantly associated with variation in energy intake, with average daily intake being 9.0 MJ for the wild‐type TT genotype and 10.0MJ for the “at risk” AT and AA genotypes, respectively.
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Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels
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