UK scientists studying the genetics of obesity in children found that FTO, a known obesity gene, also had an effect via the regulation of appetite, whereby children who had two copies of the higher risk variant did not experience sensations of fullness after eating, and this probably led them to overeat.
The study is the work of researchers at University College London (UCL) and the Institute of Psychiatry, King’s College London, and is published in the Journal of Clinical Endocrinology & Metabolism.
Variants of the FTO gene have been linked to obesity before, and in Caucasian populations it is the most commonly studied obesity gene, where findings have estimated that on average, adults with two copies of the variant are 3 kg (6.6 lbs) heavier, and adults with a single copy are 1.5 kg (3.3 lbs) heavier.
But in this study, Professor Jane Wardle, from UCL’s department of Epidemiology & Public Health, and colleagues, wanted to discover whether the gene affected obesity via consumption or use of energy.
To do this, they examined data on 3,337 UK children aged between 8 and 11 who were unrelated and whose parents had completed questionnaires about their height, weight, waist measurement, and eating habits.
The eating habits were assessed from two scales, the Satiety Responsiveness and Enjoyment of Food scales, which form part of the Child Eating Behaviour Questionnaire (which the researchers wrote has been validated against objective measures of food intake).
The researchers also genotyped the FTO gene in each child to determine which variant they carried. Using analysis of variance (ANOVA) statistical tests, they then explored the links between gene variant, appetite, and measures of obesity.
The results showed that:
- As expected, one copy of the variant (A allele) was linked to greater risk of being overweight (this was also confirmed in an independent case-control replication study of UK children of similar age).
- Children carrying both versions of the variant (AA homozygotes), had a statistically significant lower score on reduced Satiety Responsiveness (ie they found it harder to tell when they were full).
- Further analysis looking more closely at what might influence the link between carrying two copies of the gene variant and being overweight (mediation analysis), showed this was partly explained by scores on Satiety Responsiveness.
Wardle and colleagues concluded that:
“We have used a unique dataset to examine the relationship between a validated measure of children’s habitual appetitive behaviour and FTO obesity-risk genotype and conclude that the commonest known risk allele for obesity is likely to exert at least some of its effects by influencing appetite.”
The findings strongly suggest that the FTO gene influences appetite, said the researchers in a separate statement, insofar as the children who carried two copies of the higher risk variant were less likely to experience fullness when eating, as if their appetite never “switched off”.
As Wardle explained:
“While recent research has shown that the FTO gene is strongly linked with children’s body weight and food intake, this study tells us more about how the gene could be exerting its effect.”
“What we have shown is that children with the ‘risky’ variants of the gene have weaker satiety responses — meaning they don’t just overeat, but they struggle to recognise when they are full,” she added.
The researchers found that the effect of the FTO variant on appetite was independent of the children’s age, sex, socioeconomic background and body mass index (BMI).
“It is not simply the case that people who carry the risky variant of this gene automatically become overweight,” said Wardle, “but they are more susceptible to overeating.”
“This makes them significantly more vulnerable to the modern environment which confronts all of us with large portion sizes and limitless opportunities to eat,” she added.
Experts have welcomed the study, but the reaction is cautious, because the genetics of obesity is very complex. As the clinical director of the UK’s National Obesity Forum, Dr David Haslam, put it in a comment to the BBC:
“We are looking at a thousand-piece jigsaw and we have shown how the first two pieces fit together.”
He said the study was a “step in the right direction” but he didn’t want people to think that now we have the gene for obesity we can cure it:
“That is not going to happen for many years to come,” said Haslam.
“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, and Robert Plomin.
J. Clin. Endocrinol. Metab. published online June 26, 2008.
DOI:10.1210/jc.2008-0472
Source: UCL, journal abstract, BBC.
Written by: Catharine Paddock, PhD