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Obesity gene works by influencing appetite

JULY 29, 2008

New research from scientists at King’s and UCL shows that the gene associated with obesity works through effects on appetite.  The study involved over 3,000 UK children and is published in the Journal of Clinical Endocrinology & Metabolism.  This finding helps to unravel the mechanism of the genetic basis of obesity.

Previous studies have demonstrated that the gene, known as FTO, is strongly associated with obesity.  However, it was not known whether it affects weight by influencing the amount of food eaten or the amount of calories burnt off.  The results of this study strongly suggest that the gene works by modifying appetite, so that the children in the study who had two copies of the higher-risk FTO gene are less likely to have their appetite ‘switched off’ by eating.

The researchers, led by Professor Jane Wardle, UCL Epidemiology & Public Health, tested whether children carrying the higher risk gene had altered appetite in a sample of 3337 unrelated children aged 8-11 years old. This included parental reports of the children’s height, weight and waist circumference and asking parents to complete a specially-designed questionnaire about their children’s eating habits, to assess aspects such as their child’s enjoyment of food and how easily they became full.

FTO is the first common obesity gene to be identified in Caucasian populations.  Previous studies have shown that adults with two copies of the FTO gene are on average 3kg heavier, and individuals with a single copy are on average 1.5kg heavier, than those without the gene. 

Lead author of the study, Professor Jane Wardle, UCL Epidemiology & Public Health, said: “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.  Importantly, the effect of FTO on appetite is the same regardless of the age, sex, socioeconomic background or body mass index of the children.

“It is not simply the case that people who carry the risky variant of this gene automatically become overweight – 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”

The co-author on the paper, Claire Haworth in the MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry at King’s commented: “It is exciting to come closer to understanding how the FTO gene might affect obesity.  This research suggests that the genetic risk comes from not recognizing signs of being full after eating (satiety), which is also exciting because it suggests ways in which this research can be translated into treatment and prevention." 

 The study is based on Professor Robert Plomin's' Twins Early Development Study (TEDS) in which Ms Haworth is also involved.   This study, which is MRC funded, began in 1995 and has followed more than 5000 pairs of UK twins from birth through adolescence. 

The paper ‘Obesity-associated genetic variation in FTO is associated with diminished satiety’ (doi:10.1210/jc.2008-0472) has been published online ahead of print by the Journal of Clinical Endocrinology & Metabolism, and can be accessed at:  

The study was funded by Cancer Research UK, the Medical Research Council and the Wellcome Trust and carried out by researchers at UCL, King’s College London and the University of Cambridge.
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