Obesity Gene Variants Predict Overeating in Slim Children

Marlene Busko

May 30, 2019

Children who were not obese and were allowed to eat as much as they wanted of a lunch of familiar foods ate more if they had certain fat mass- and obesity-associated (FTO) gene variants.

Specifically, children with the AT obesity gene variant consumed 64 more calories than children with the TT variant, and children with the AA variant consumed 128 more calories than children with the TT variant — after adjusting for body weight and calories eaten in the previous meal.

"Even though [64] calories is not a lot per se, if this pattern generalized to multiple meals per week or day, this increased caloric intake can add up over time and may contribute to gaining excess weight," senior study author Michael Rosenbaum, MD, Division of Molecular Genetics, Department of Pediatrics, Columbia University Irving Medical Center, New York City, said in a statement issued with the article that was published online May 22 in Obesity.

The "results corroborate and extend prior work [in children and adults with obesity] by showing a dose-dependent effect [of A alleles of the FTO gene] on food intake in children without obesity," conclude the researchers, led by Lisa M. Ranzenhofer, PhD, Columbia University Irving Medical Center and New York State Psychiatric Institute.

"Early identification of the physiology and behaviors that constitute early risk factors for subsequent weight gain will help inform best practices for intervention and prevention of obesity in children," according to Rosenbaum.

Would Slim Children With Gene Variant Eat More?

In previous research, single-nucleotide polymorphisms of the FTO gene have been linked with an increased risk of obesity, although not in African Americans.

About 70% of the population has at least one A allele, which is associated with an increased risk of obesity: about 14% to 18% of the population is homozygous (AA allele), while 29% to 50% is heterozygous (AT allele), and the remaining 30% to 35% are homozygous for the T allele (TT), which is not associated with an increased risk of obesity.

However, previous studies were of children and adults who were already overweight or obese, so it was not clear from previous findings if slim children with the gene variants associated with increased risk of obesity would eat more than other children, or choose more high-calorie foods, in a standardized laboratory meal.  

To investigate this, researchers recruited and enrolled 122 children aged 5 to 10 with a body mass index (BMI) at or below the 95th percentile for their age and sex who lived in New York City.

The children were a mean age of 8.5 years and about half were boys.

They were instructed not to eat or drink anything (other than water) after 10 pm on the night before the study day.

On the study day, the children were weighed and measured, and they provided a saliva sample for DNA testing.

They were given a standardized breakfast of Cheerios or cornflakes with milk.

After 3.5 hours, they were given a choice of 28 traditional foods and beverages for lunch that they were not allergic to (including chicken nuggets, sandwich items, fruits and vegetables, salty snacks, and desserts).

The children were instructed: “This is your lunch for today. You may eat as much as you would like, but you do not have to eat anything you do not like.”

They were able to watch cartoons while they ate, and they were instructed to press a bell when they were finished (within an hour).

In line with what was expected, 25 children (20.5%) had the FTO AA genotype and 53 children (43.4%) were AT. The other 44 children (36.1%) were TT.

Children in the three genotype groups had similar mean age, weight, and height.

For each FTO A allele, the children consumed 64 more calories in the laboratory lunch than was predicted based on their body weight and the calories they consumed at breakfast.

There was no association between FTO genotype (AA, AT, or TT) and the proportion of calories from fat or carbohydrate or protein the children consumed.

There were too few African American children (27 children) to be able to analyze genotype differences in this subgroup.

Each Copy of A Allele Predicted Additional 85 Calories in Non-Blacks

However, in non-African American children, each copy of the A allele predicted an additional 84.9 calories eaten (P = .02), which was greater than in the whole cohort — suggesting that the FTO genotype is not associated with adiposity in African Americans.

"Our data suggest that the potential mechanism of weight gain associated with the FTO gene relates to an increase in overall intake and not a preference for highly palatable foods," Ranzenhofer and colleagues summarize.

"However, it does not define potential underlying mechanisms such as alterations in reward value of food, general increased impulsivity, or impulsivity specifically to food."

This remains to be determined in further research, they say.

"The ultimate goal is to prevent the at-risk child or the child who has obesity from becoming an adult with obesity," concluded Rosenbaum.

The study was funded by grants from the National Institutes of Health. The authors have reported no relevant financial relationships.

Obesity. Published online May 24, 2019. Full text

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