July 15, 2013

expert reaction to obesity gene, ghrelin hormone levels and brain responses to images of food

A study in the Journal of Clinical Investigation found that people with the a variation of the FTO gene have higher circulating levels of the ‘hunger hormone’, ghrelin, in their blood,  meaning they start to feel hungry again soon after eating a meal. 

Professor Steve Bloom, Head of Division of Diabetes, Endocrinology and Metabolism, Imperial College London, said:

“We know the tendency to overeat in a society with too much food and no need for exercise is inherited.  Fat parents have fat children even if they grow up in other thin families (orphans) and thin parents’ children stay thin even in a fat family environment.  Inheritance is estimated to explain up to 75% of obesity in an obesogenic environment.  What are the obesity genes?  Here we have had difficulty – big surveys have not come up with a clean “obesity gene”.  It seems it is polymorphic i.e. a cluster of many genes is responsible.  This isn’t unexpected as, actually, in wild man if you didn’t get fat in the summer you died in the winter.  So a certain level of obesity when berries were plentiful was essential to survival, even through the next famine.

“So, the only really concrete genetic change related to obesity that has been found is the FTO polymorphism.  It had, hitherto, no known mechanism.  This group have now identified that the “hunger hormone”, ghrelin, released from the stomach when you haven’t eaten, is not suppressed in the normal manner by eating if you have the FTO form associated with obesity – it remains higher than in normal subjects.  This in turn will tend to lead people to eat more food and gain weight.  It isn’t an enormous effect but the FTO gene polymorphism isn’t responsible for more than a small percentage of the obesity epidemic, it is merely the best marker we have found in an otherwise confusing situation.

“Slowly we are discovering the factors which make us overweight and this study, encompassing not only demonstration of a higher level of hunger hormone, ghrelin, but also changes in the brain associated with ghrelin’s action, is an important step forward.  Already pharmaceutical companies are working on ghrelin antagonists and this will further spur on that effort and perhaps indicated whom best to treat.”

Professor Sir Stephen O’Rahilly, Professor of Clinical Biochemistry and Medicine, University of Cambridge Metabolic Research Laboratories, said:

“We have known for a while that 16% of the UK population have 2 copies of the A variant of the FTO gene. They carry, on average, 3 kilos more fat than people who carry no copy of the A variant. Elegant studies in large numbers of children have established that the excess weight is driven by an increased drive to eat. This new study opens up the possibility that the FTO A allele influences appetite by increasing both the amount of the appetite stimulating hormone ghrelin in the blood and the sensitivity of the brain to ghrelin. It is somewhat surprising that such major effects on ghrelin levels, and on the brain’s response to food, were detectable in such small numbers of subjects, as the effects of the FTO A allele on energy balance must be quite subtle resulting, as it does, in only a few kilograms of excess fat after a lifetime of exposure to the gene. So further research will be required in order to determine the extent to which effects on the ghrelin axis can explain the effects of genetic variation in FTO on obesity risk.”

‘A link between FTO, ghrelin, and impaired brain food-cue responsivity’ by Efthimia Karra et al., published in the Journal of Clinical Investigation on Monday 15 July 2013.