HYPERACTIVE AFP gene causes eating and obesity

PharmaLive.com (16 November 2010) - scientists have gained strong confirmation of the direct connection between the AFP gene and obesity, obtaining the first direct evidence that the hyperactivity of the gene leads to eat and obesity in mice.

University of Oxford and the Council of medical research (MRC), the Wellcome Trust and the MRC funded research team have published their results in the journal Nature Genetics.

Results team of suggested that the gene may be a promising target for the development of anti-obesity drugs that Act by turning to the activity of the gene.

"This work we confident that the AFP is an important gene that contributes to obesity," said Frances Ashcroft the Professor of the Oxford University Department of Physiology, Anatomy and genetics, and one of the leaders of research. "Too much activity of this gene can lead to put on weight by overeating.

"We now think the development of drugs that turn down the activity of AFP gene in the form of pills potential anti-obesity b.c ' is a long way off the coast and there is no guarantee of success, but it is an attractive prospect,' she adds."

In 2007, an international team of researchers, including Oxford, scientists announced that they had identified the first genetic variant that may be linked to an increased risk of obesity in a large genome-wide study.

The only change in the DNA sequence of lay of AFP gene.Persons with two copies of this variant genetic (approximately 16% of the population of European origin were two copies) have been the heaviest 3 kg on average than those without.

While it is an important result, genome-wide association studies are often first step allowing then detail to identify the mechanisms behind the observed connection in this case to obesity research.

In particular, surveys genome-scale cannot be certain identified genetic variation directly increases the risk of obesity .the change in DNA could be an indicator or a marker important gene is located nearby, or DNA modification could lie in a control element that regulates a different gene distance.

Researchers of the study, led by Mr. Roger Cox MRC Harwell and Professor Frances Ashcroft, Oxford University, set out determine if there were differences in the activity of the gene of OTF itself directly causing the increase in body weight.

Scientists mimic mice with extra copies of the AFP gene.These mice were in good health, but eat more and becoming fatter than normal mice.

Female with two additional copies of the gene AFP, when subjected to a standard diet, mice has become 22% heavier than normal female mice after 20 weeks.The difference in weight for male mice was 10 lined researchers have also show that the difference came because the mice with AFP hyperactivity consume more food.(There is no suggestion that differences in humans with variants of the AFP weight are or could be almost as large or necessarily affect gender in a similar proportion.)

Chris Church, MRC Harwell and author of the study PhD student, said: "for the first time, we have provided convincing evidence that the FTO gene causes obesity .the ' next step is to understand how it performs, for example if it increases the appetite by influencing our brains or modifies messages from our reserves of fat and other times we know how AFP causes obesity tissus.Une, we have the opportunity to seek to develop drugs for treatment."

Genome-wide association studies did a fantastic job narrowing zones in the genome of the head of obesity.They have provided guides from the place to go, but these areas remain pinning a specific gene as we've done here for the first time with the AFP.Mouse model has allowed us to achieve this goal in only a few years, and we hope the same process will now apply to other areas of genes involved in obesity, allowing scientists to confirm precisely that other genes may predispose us to become overweight.»

From 1 to 3 persons in the United Kingdom are obese or .the ' obesity predisposes people to many diseases, including heart disease, type 2 diabetes and the estimated amount cancer.Le of obesity in the NHS is approximately 1 billion pounds per year, with an additional £ 2.3 to 2.6 billion pounds per year to the economy as a whole.

"This gene is the novel research on obesity and it will be interesting to know how it works," explains Mr Roger Cox, unity of genetics in mammals of the Council of medical research at Harwell and one of the leaders of research. "We now have to address these issues mouse models.»

Editor's note: this article is not intended to provide medical advice, diagnosis or treatment.

Source of the story:

The story above is reproduced (with drafting adaptations by staff at PharmaLive.com) materials provided by The University of Oxford.

Reference of the review:

Chris Church, Lee Moir, Fiona McMurray, Christophe Girard, Gareth T Banks, Lydia Teboul, Sara Wells, Jens C Brüning, Patrick Nolan, Frances M Ashcroft, Roger D. Cox.Tre overexpression leads to an increased food intake and gives rise to obesity .Nature Genetics, 2010; DOI: 10.1038/ng.713

Note: If no author is given, the source is cited for this.

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