1 in 4 White people are fat because... they're White... oh and genetics

Famished gene is found and could help tackle obesity
By Roger Highfield, Science Editor
Last Updated: 10:01am BST 07/07/2008




A genetic change that makes white people feel famished has been found in research that could help predict the children at risk of obesity and develop new treatments.

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The common DNA mutation was found in people of European ancestry and the find reveals that a minor change can have a significant impact on the production of several hormones controlling our appetite, which scientists say is "definite evidence that common obesity is a disease of the appetite and satiety."

advertisementThe mutation, each copy of which raises the risk of obesity by 50 percent, is found in around one person in every four white people, according to research published today in Nature Genetics by an international team led by Imperial College London.

Understanding this mechanism will help scientists to develop new treatments, notably by making obese people feel full.

The gene, called PCSK1, is the recipe for the body to make the "proconvertase enzyme", which is responsible for producing fully functioning versions of hormones such as insulin, glugagon and melanocortin. These are all involved in controlling the rate of metabolism.

Changes in the PCSK1 gene cause relatively minor abnormalities in the enzyme that can have a major effect on the way the body responds to the hormones, which all play a major role in regulating weight.

The discovery was made by Prof Phillipe Froguel of Imperial with colleagues there and in France, Denmark, Sweden and Germany, after screening the genetic makeup of over 13,000 people. They discovered a significant association between the genetic mutation in PCSK1 and a tendency to develop obesity. These variants were also associated increased risk of childhood obesity.

"This is the first time that we have found a strong link between common mutations and common obesity in the PCSK1 gene," says Professor Froguel.

"We know that common forms of obesity depend on variations in multiple genes, so this is an important addition to the list of genes we need to consider as therapeutic targets for treatment in the future."

Many genes have now been linked to obesity including MC4R reported by Prof Froguel’s team in March 2008 and FTO, reported by the same team and independently by an Oxford group.

"We believe that very soon we’ll have a large part of the obesity genetic puzzle, each piece modestly increasing obesity risk (of 20 to 50%) and weight (two to four kilograms per mutation) but it makes a real difference for those who carry many of them."

"All these genes so far (including the putative new ones) are in our brain. Obesity is not so far a disease of excessive storage (energy intake being equal) but rather a problem in controlling appetite," he said.

"It is more related to our will to eat than to the greed of our adipose cells to store energy. Even if the latter exists (and there are twin studies to show it does) in my view it more something controlled by our brain than a pure fat issue. In other words the solution is in improving human behaviour (especially children at high genetic risk) and possibly new drugs acting on the behaviour."

The problem with targetting this gene and enzyme with drugs is that side effects are likely, though he said that developing small chunks of protein, called peptides, to target the appetite mechanisms of the brain is one possibility. He said that a colleague at Imperial, has taken a similar appproach.

"Prof Steve Bloom has developed a small company to develop these anorexic peptides and it is very interesting that my totally independent research using genetics to elucidate physiology came to same conclusion."

Prof Bloom has found a way to boost the body’s existing levels of oxyntomodulin, which is normally released from the stomach as food is consumed, signalling to the brain that the body’s need for food has been satisfied.

One in four Britons is now classed as obese, one in three 10-year-olds is either overweight or obese and more than one million obesity drugs are prescribed every year. Experts estimate that by 2050 half of all adults will be classed as clinically obese.