A unique study examining a small but carefully matched group of participants and using neuroimaging provides insights into how the FTO gene interacts with ghrelin – the ‘hunger hormone’ - in order to modify the way in which the brain controls appetite.
FTO was the first gene to be robustly identified with common (polygenic) obesity. Around one of six of the UK population carries two copies of the obesity risk version of the FTO gene, which is associated with increased food intake and decreased satiety. It is widely expressed throughout the body, especially in the brain.
Researchers studied two groups of participants – those with the two copies of the high obesity-risk FTO variant and those with the low obesity-risk version. They matched the volunteers perfectly for body weight, fat distribution and social factors such as educational level to ensure that any differences they saw were linked to FTO, and not to other physical or psychological characteristics.
By testing blood cells, the study found that people with the obesity-risk FTO variant have higher circulating levels of ghrelin in their blood after eating. Using functional magnetic resonance imaging (fMRI) to examine how the brain responds to images of high and low calorie foods the scientists also found that individuals with the obesity-risk FTO variant rated pictures of high-calorie foods as more appealing after a meal than the low-risk group. Researchers concluded that people with the obesity-risk FTO variant are biologically programmed to eat more.
Comment: This study helps us better understand the nature of FTO-related obesity. However, the effects of the FTO A allele are subtle, accounting for only around 3kgs additional body fat over a lifetime and therefore play only a very small part of the current obesity epidemic, although the new research highlights the complexity of interactions between genes and the environment and their combined impact on body weight.
In our recent report, Genomics of Obesity, we find that obesity susceptibility genes such as FTO are increasingly expressed in the context of an obesogenic environment – that is, one where the norm is to consume energy-dense food but there is little need to engage in energy expending activities. Common obesity is therefore the product of both multiple contributory genetic factors and the physical and social environment.