I am impressed by the progress being made by some of my former colleagues who are busily unraveling the complex genetics of obesity.
In a paper in the journal Science a group of British scientists including Chris Ponting of the Medical Research Council Functional Genetics Unit in Oxford and Stephen O'Rahilly’s group at the University of Cambridge, has made a second breakthrough in twelve months in understanding how a gene triggers weight gain in some individuals. In May we looked at the first piece of work on the gene called “FTO.”
At that time we learned that variations in the FTO gene influence people's risk of becoming obese. This particular gene was of great interest because the genetic variant in FTO that predisposes to obesity is very common in the population.
About half the British population carries a copy of the variant and they are on average 3-4 pounds heaver than those who do not have it. The 16 per cent of the population who carry two copies of the variant and are on average 6-7 pounds heavier. We also learned that carriers of the variant have an increased risk of diabetes. However the function of FTO was completely unknown.
The new paper shows that the FTO gene codes for an enzyme - 2-Oxoglutarate-Dependent Nucleic Acid Demethylase - that can act directly on DNA. This strongly suggests that FTO might have a role in controlling how and when genes are turned on and off.
The investigators also found that FTO is highly expressed in the hypothalamic region of the brain, which has important roles in the control of hunger and satiety. In certain areas of the hypothalamus, the levels of FTO are influenced by feeding and fasting.
This is a remarkable finding. That a gene involved in obesity and diabetes has a direct effect on DNA in specific regions of the brain is very exciting. It suggests that the gene is involved in influencing how well the brain senses hunger and fullness. Small molecules derived from metabolism can modulate the activity of FTO, so we can see a direct link form food to metabolism to DNA in the brain.
The findings raise all kinds of treatment possibilities and also confirm something that I have been teaching for three decades: weight control does not start with a diet. It starts between the ears. Until you have been shown how to re-program your brain, thoughts and emotions, your chance of successfully controlling your weight is, ahem, slim.