Human obesity: FTO, IRX3, or both?

Cedernaes, Jonathan

doi:10.1016/j.molmet.2014.05.003

Cited by 9 publications

(7 citation statements)

References 10 publications

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“…A hypothesis could be that FTO expression in human brain regions, implicated in feeding conditions and regulation of energy expenditure, such as the hypothalamus and/or brainstem, could be differentially regulated depending on FTO genotype. Differential effects may be evident for FTO expression depending on its polymorphism under more dynamic settings, such as following food cue exposure or longer dietary interventions (Cedernaes & Benedict, ).…”

Section: Discussionmentioning

confidence: 99%

Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

González-Herrera

Zavala-Castro

Ayala-Cáceres

et al. 2018

American J Hum Biol

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Objectives Genetic variation of the fat mass and obesity associated gene (FTO) has been identified as a risk factor for obesity and obesity traits. Distribution of FTO single nutleotide polymorphisms (SNPs) rs1421085T>C, rs9939609T>A, rs8057044G>A and copy number variation (CNV) was evaluated in association with childhood obesity or overweight status in children with Mayan ethnicity. Methods We included 318 school‐aged children with obesity or overweight status (body mass index [BMI]: >85th percentile) and 303 children with normal weight (BMI: 15th‐85th percentile). Genotyping was performed using real‐time polymerase chain reaction (RT‐PCR) with TaqMan probes. The cross‐sectional study was carried out using univariate and multivariate logistic regression models adjusted for gender. Results FTO‐SNP rs1421085 showed significant differences between children with obesity and children with normal weight for the heterozygous genotype (P = 0.003) and for allele frequencies (P = 0.023). Adjusting by gender, significant differences were found in frequencies of the hetezygous genotype of SNPs rs9939609 (P = 0.023) and rs1421085 (P = 0.003) as well as in allele frequencies (P = 0.042 and P = 0.013, respectively) between girls with obesity and girls without obesity. In contrast, SNP rs8057044 was significantly different only between heterozygous overweight versus normal weight boys (P = 0.035) and for the allele frequency of rs8057044 (P = 0.021). The mean relative CNV was significantly higher in male overweight children than in boys with normal weight (P = 0.000). Conclusions The FTO SNP rs1421085 is a genetic factor associated with obesity in Mayan school‐aged children. FTO SNPs rs1421085 and rs9939609 affect genetic susceptibility for obesity only in girls, whereas, SNP rs8057044 and CNV are associated with overweight status only in boys.

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Section: Discussionmentioning

confidence: 99%

Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

González-Herrera

Zavala-Castro

Ayala-Cáceres

et al. 2018

American J Hum Biol

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“…Interestingly, a recent study ( 9 ) has challenged the established view of FTO as the major gene associated with BMI and risk of obesity, reporting that the region of FTO intron 1 harboring the BMI-associated variants are strongly associated with IRX3 gene (500 kbp downstream of FTO intron 1) expression in cerebellar brain samples. However, it has been pointed out that the cerebellum is not primarily involved in food intake or appetite regulation and FTO expression may function in a site-dependent manner ( 72 ). In addition, another study ( 10 ) suggested that RPGRIP1L, located >100 bp 5′ in the opposite transcriptional orientation of FTO , may be partly or exclusively responsible for the obesity susceptibility signal at the FTO locus.…”

Section: Discussionmentioning

confidence: 99%

Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of Over 16,000 Children and Adolescents

Downer

Kilpeläinen

et al. 2015

Diabetes

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The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.

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“…Our results provide a direct link between obesity gene variant and kidney fibrogenic responses, which could be a possible key for future therapeutic choice. Although recent data suggested that Irx3 is a functional target of variants within introns of FTO 36 , the exact role of FTO or IRX3 in human obesity is still unclear 37 . The role of IRX3 in kidneys also remains unknown.…”

Section: Discussionmentioning

confidence: 99%

FTO modulates fibrogenic responses in obstructive nephropathy

Wang

Shie

Tsai

et al. 2016

Sci Rep

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Genome-wide association studies have shown that variants in fat mass and obesity-associated (FTO) gene are robustly associated with body mass index and obesity. These FTO variants are also associated with end stage renal disease and all-cause mortality in chronic kidney diseases. However, the exact role of FTO in kidneys is currently unknown. Here we show that FTO expression is increased after ureteral obstruction and renal fibrosis. Deficiency of the FTO gene attenuates the fibrogenic responses induced by ureteral obstruction in the kidney. Renal tubular cells deficient of FTO produce less α-SMA after TGF-β stimulation. FTO is indispensable for the extracellular matrix synthesis after ureteral obstruction in kidneys. Indeed, global gene transcriptions amplitude is reduced in FTO deficient kidneys after ureteral obstruction. These data establish the importance of FTO in renal fibrosis, which may have potential therapeutic implications.

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Human obesity: FTO, IRX3, or both?

Cited by 9 publications

References 10 publications

Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of Over 16,000 Children and Adolescents

FTO modulates fibrogenic responses in obstructive nephropathy

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