Note: The Messenger of Allah says: “The son of Adam will never fill a container with something worse and evil than his stomach. It will suffice him some morsels (food) that will keep him on his feet, otherwise, he should divide his stomach into three parts: one third for his food, the other for his drink and the other third for his breath.” (Ibn Hibban)
A gene that makes people vulnerable to obesity also produces a protein that may directly modify DNA in a region of the brain known to control food intake. Theunexpected finding sheds light on how gene variants can predispose individuals to obesity, say scientists.
Earlier this year, analysis of blood samples from nearly 40,000 individuals linked certain variants of a gene called FTO with a 70% increased risk of obesity. Those people who carried two defective copies of the FTO gene were 3 kilograms heavier on average than their counterparts with normal versions of the gene. The biological function of the FTO gene, however, remained a mystery.
To help solve this puzzle, Frances Ashcroft at the University of Oxford, UK and her collaborators took a close look at the sequence of the gene. Using a complex algorithm, they searched for similar sequence fragments within the human genome.
The hunt for possible matches revealed that the FTO gene most closely resembles the genetic sequence of the “2-OG oxygenase” family of proteins. These proteins have several roles, including the repair and modification of DNA.
Ashcroft and her colleagues 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 toswitch genes on or off, so altering 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.
In another part of the new study, researchers examined the brains of micedesigned 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. Ashcroft says it is still unclear how the FTO protein directly influences appetite, but it 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. But he stresses that these 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.”