FTO genotype impacts food intake and corticolimbic activation

Melhorn, Susan J.; Askren, Mary K.; Chung, Wendy K.; Kratz, Mario; Bosch, Tyler A.; Tyagi, Vidhi; Webb, Mary F.; Leon, Mary Rosalynn B. De; Grabowski, Thomas J.; Leibel, Rudolph L.; Schur, Ellen A.

doi:10.1093/ajcn/nqx029

Cited by 73 publications

(74 citation statements)

References 53 publications

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“…Our primary significant finding that the FTO risk‐allele dose is associated with overall caloric intake during a laboratory meal in children replicates prior child and adult studies and extends existing knowledge to a pediatric sample without obesity. It demonstrates that rs9939609 is associated with biological processes and behaviors essential to the development of excess weight gain rather than those resulting from a state of obesity.…”

Section: Discussionsupporting

confidence: 77%

“…Consistent with one prior study in children but in contrast to others , our data did not suggest that allelic dose affects food choices (proportional consumption of fat calories, dietary energy density, or diet variety). A similar study in an adult population, most of whom had obesity , also reported no difference in dietary macronutrient composition consumed despite a 350‐kcal difference in overall intake predicted by the AA genotype compared with the AT/TT genotype. Other recent studies of self‐reported dietary intake in adults have suggested a small but significant impact of the risk allele on protein intake .…”

Section: Discussionmentioning

confidence: 83%

“…The neuro‐molecular mechanisms underlying genotypic effects are under intense scrutiny in cell‐based and animal models and by use of functional magnetic resonance imaging in humans. There is some evidence of genotypic differences in central nervous system reward or satiety pathways during exposure to highly palatable food pictures (e.g., amygdala, medial orbitofrontal cortex, ventral tegmental area, striatum, nucleus accumbens) , suggesting hyperresponsivity in those with the obesity‐promoting allele. Melhorn et al found that AA adults self‐reported less fullness and rated highly palatable food pictures as more appealing than AT/TT adults.…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence of genotypic differences in central nervous system reward or satiety pathways during exposure to highly palatable food pictures (e.g., amygdala, medial orbitofrontal cortex, ventral tegmental area, striatum, nucleus accumbens) , suggesting hyperresponsivity in those with the obesity‐promoting allele. Melhorn et al found that AA adults self‐reported less fullness and rated highly palatable food pictures as more appealing than AT/TT adults. In terms of molecular mechanisms, the intronic sequence variants in FTO have been shown to affect the expression of numerous genes and possibly FTO itself.…”

Section: Discussionmentioning

confidence: 99%

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The FTO Gene and Measured Food Intake in 5‐ to 10‐Year‐Old Children Without Obesity

Ranzenhofer

Mayer

Davis

et al. 2019

Obesity

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Objective: Genetic variation in the first intron of FTO (e.g., single-nucleotide polymorphism [SNP] rs9939609) is strongly associated with adiposity. This effect is thought to be mediated (at least in part) via increasing caloric intake, although the precise molecular genetic mechanisms are not fully understood. Prior pediatric studies of FTO have included youth with overweight and obesity; however, they have not informed whether a genotypic effect on ingestive behavior is present prior to obesity onset. Therefore, this study investigated the association between FTO and caloric intake in children aged 5 to 10 years without obesity (adiposity ≤ 95th percentile). Methods: A total of 122 children were genotyped for rs9939609 and ate ad libitum from a laboratory lunch buffet following a standardized breakfast. Linear regressions, adjusting for body mass, were used to examine the association between FTO "dose" (number of copies of SNP rs9939609) and intake variables. Results: There was a significant association between FTO and total intake. Each risk allele predicted an additional 64 calories, accounting for 3% of the variance. There were no associations between FTO and macronutrient preference, energy density, or diet variety. Results were influenced by race. Conclusions: Results corroborate and extend prior work by showing a dose-dependent effect on food intake in children without obesity.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The FTO Gene and Measured Food Intake in 5‐ to 10‐Year‐Old Children Without Obesity

Ranzenhofer

Mayer

Davis

et al. 2019

Obesity

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“…15 The m 6 A is a prevalent internal modification of messenger RNA (mRNA), regulating gene expression 16 ; thus, its demethylation plays an important role in mRNA processing. 17 People with FTO risk alleles are predisposed to obesity probably as a result of impaired central satiety processing and increased food intake 18,19 together with a preference for high-calorie foods. 20,21 FTO gene may also be involved in the regulation of adipogenesis, 17,22 lipolysis 23 and adipocyte thermogenesis.…”

Section: Introductionmentioning

confidence: 99%

The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland

Zdrojowy-Wełna¹,

Bednarek-Tupikowska²,

Zatońska³

et al. 2020

Adv Clin Exp Med

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The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland Abstract Background. Fat mass and obesity-associated gene (FTO) polymorphism remains the strongest known genetic determinant of common obesity. However, its influence depends on ethnicity, and the FTO-mediated predisposition to other metabolic disturbances is questionable.Objectives. The aim of our study was to evaluate the association between FTO rs9939609 polymorphism and metabolic syndrome in a population of Prospective Urban Rural Epidemiology (PURE) study in Poland.Material and methods. We enrolled 1,097 participants of the PURE study (683 women and 414 men) from the Lower Silesian voivodeship. Anthropometrical parameters and blood pressure were measured. Blood samples were taken for an examination of lipid profile and fasting glucose level. Genomic DNA was isolated and FTO polymorphism rs9939609 was genotyped.Results. Male A-allele carriers had significantly higher mean body mass, body mass index (BMI), waistto-hip ratio (WHR), and waist and hip circumferences than men without risk allele. They were also more often diagnosed with obesity on the basis of BMI and central obesity parameters. No such influence was observed in women. There were no significant associations between FTO polymorphism and metabolic syndrome or its components. Conclusions.Our results suggest a sex-specific association between FTO polymorphism and obesity traits. The occurrence of metabolic syndrome or its components was not related with FTO gene variation in our cohort.

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Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men

Berkseth

Rubinow

Melhorn

et al. 2018

Obesity

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Objective: To determine whether a relationship was evident between gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men Methods: 41 adult men (ages 18–50 years) from 23 twin pairs underwent fasting morning blood draw and brain MRI. T2 relaxation time was used to quantify gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17β-estradiol were measured by LC-MS/MS. Body composition including visceral adiposity was measured by dual X-ray absorptiometry. Results: A negative association was found between MBH T2 relaxation time and plasma concentrations of both free and total testosterone ( r = −0.29, P<0.05 and r = −0.37, P<0.01, respectively). Visceral adiposity exhibited a negative correlation with plasma total testosterone concentration ( r = −0.45, P=0.001) but a positive correlation with MBH T2 relaxation time ( r = 0.24, P=0.03). The negative correlation between plasma total testosterone and MBH T2 relaxation time remained significant after adjustment for visceral adiposity, age, BMI, and insulin resistance. Conclusions: In healthy men across a range of BMIs, MBH gliosis was associated with higher visceral adiposity but lower endogenous testosterone. These findings suggest that MBH gliosis could provide novel mechanistic insights into gonadal dysfunction in men with obesity.

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FTO genotype impacts food intake and corticolimbic activation

Abstract: The findings are consistent with a model in which allelic variants in FTO raise obesity risk through impaired central nervous system satiety processing, thereby increasing food intake. This study is registered at clinicaltrials.gov as NCT02483663.

Cited by 73 publications

References 53 publications

The FTO Gene and Measured Food Intake in 5‐ to 10‐Year‐Old Children Without Obesity

The FTO Gene and Measured Food Intake in 5‐ to 10‐Year‐Old Children Without Obesity

The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland

Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men

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