Obesity gene may alter DNA in the brain region that controls food intake

November 14th, 2007 - 10:21 am ICT by admin  

The scientists believe that their findings may help better understand how gene variants can predispose individuals to obesity.

Earlier this year, an analysis of blood samples from nearly 40,000 individuals was carried out. As a result of it, scientists discovered that certain variants of a gene called FTO increased the risk of obesity by 70 per cent.

During that study, people who carried two defective copies of the FTO gene were found to be 3 kilograms heavier on average than their counterparts with normal versions of the gene. However, the biological function of the gene remained a mystery.

In the present study, Frances Ashcroft at the University of Oxford and her colleagues took a close look at the sequence of the gene. They used a complex algorithm to searched for similar sequence fragments within the human genome.

It was found that the FTO gene most closely resembles the genetic sequence of the “2-OG oxygenase” family of proteins, which have several roles such as the repair and modification of DNA.

The researchers synthesised the FTO protein in the laboratory using the human sequence and mixed the protein with single-stranded DNA in a test tube. They found that the protein removed chemical markers on the DNA, known as methyl groups.

This is significant, as the addition and removal of methyl groups can act to switch genes on or off, and thereby alter their activity. This process is known as ‘epigenetic’ change.

The researchers believe that the FTO protein may somehow modify the activity of genes involved in metabolism and fat storage, which in turn may influence a person’s risk of obesity.

As part of the same research, the researchers also examined the brains of mice designed to produce fluorescent FTO proteins. They found high concentrations of the protein in the rodents’ hypothalamus, a region of the brain that helps regulate hunger.

Though Ashcroft admits that it is yet to be understood how the FTO protein directly influences appetite, she says that the gene could possibly be exerting influence by altering the activity of other genes.

Alan Herbert, a geneticist at the Boston University School of Medicine in Boston Massachusetts, US, says that certain FTO variants might work in the brain to increase fat storage throughout the body.

He, however, says that such variants could have been helpful for our ancestors, who had less reliable food supplies.

“At some point in history, it was likely advantageous to efficiently store calories,” New Scientist magazine quoted him as saying. (ANI)

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