Genetic variants link obesity to behaviour
17 December 2008
“It might seem remarkable that it is the brain that is most commonly influenced by genetic variation in obesity, rather than fat tissue or digestive processes,” says Dr Inês Barroso, a senior author on the study, from the Wellcome Trust Sanger Institute.
“Until 2007, no genetic associations had been found for ‘common obesity’, but today almost all those we have uncovered are likely to influence brain function.”
The findings are the result of a genetic study of more than 90 000 people. The researchers identified a total of six variants - five affecting the brain - that are linked to increased body mass index (BMI), the most commonly used measure of obesity.
The body increases in weight when calories taken in exceed calories burned. But behind that simple equation lie behavioural processes such as appetite and satiety, as well as the biochemical mechanisms our bodies use to process foods and use stores of energy such as fat.
A part of the brain called the hypothalamus controls many of our basic functions such as body temperature, hunger and fluid balance, and is programmed to maintain the status quo.
“Very occasionally, mutations in genes active in the hypothalamus have dramatic consequences for weight gain such that people carrying these mutations are severely obese,” says Dr Ruth Loos, one of the authors, from the Medical Research Council Epidemiology Unit.
“Such mutations might be considered exceptional. However, we suggest that the picture for common obesity is very similar. Many or most genes associated with increased BMI are active in the brain.”
Previous studies in twins suggest that genetics can account for 40-70 per cent of the variation in BMI. Yet only one previously discovered gene was thought to be linked to increased BMI or obesity in humans.
The new gene candidates provide a rich pool of resources to help us understand some of the processes in the brain that drive increased BMI and common obesity.
By identifying genetic variants that affect obesity, researchers hope to understand better the mechanisms regulating energy balance, which will guide the development of new therapies and improve diagnosis.
The study is published in ‘Nature Genetics’ by the GIANT Consortium and includes authors from more than 60 institutions.
Image: Overweight women out shopping; Libby Welch, Wellcome Images
References
Willer C J et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet [Epub ahead of print 14 December 2008]; DOI:10.1038/ng.287