Posted by: Neurobites | May 15, 2010

FTO and the Genetics of Obesity

Hello!  This is Harry, and I’ll be starting Neurobites off right with a series of posts about Fto, a gene that is making news for its relation to obesity in humans.  Stay tuned for more posts in my Fto series, and post a comment!

The basic distinction between “nature” and “nuture” invariably becomes far more nuanced once it enters the focus of a serious scientific investigation.  In the post-genomic world, discoveries concerning the link between complicated traits and genetics are ever increasing in frequency, yet it is only on rare occasions that a single gene can be unambiguously linked to the development of such a trait.  More often than not, it is a complicated interaction between genes and environment that gives rise to the traits we are interested in.

The search for a particular gene that could be implicated in the development of obesity has been largely fruitless.  Humans can vary in their weight and body composition for a number of different reasons including metabolism, stress, availability of food, and so forth.  Thus it is difficult for large scale studies to make links between particular genetic variations and gross markers of obesity such as BMI and waist size, since both of those traits are final common pathways of any number of different perturbations.

In 2007, researchers began to notice that people carrying a particular version of the Fto gene had a higher Body Mass Index (BMI) than the general population.  This type of genetic variation is called a Single Nucleotide Polymorphism (SNP).  In this case, the difference between the common version of the gene and the “risk” version of the gene comes down to a single nucleotide – the smallest unit of difference possible at this level.  People who carry two copies of the “risk” version of this gene are, on average, three kilograms heavier than people who carry the other version of this gene.  This gene is higher in certain populations than in others, but in Western European cultures the prevalence reaches around 46%.

Fto is expressed widely throughout the body.  Fto is found in diverse tissues such as fat, muscle, and the pancreas.  Interestingly, Fto is also expressed in the hypothalamus, a region of the brain critical in regulating, among other things, appetite and metabolism.  If individuals harboring the “risk” version of Fto had problems with this system, it may explain part of the genesis of obesity.  So we have good evidence that having a certain version of the Fto gene is a risk factor for obesity in humans, and we know that Fto is active in parts of the brain that regulate appetite and metabolism.  Many questions still remain, and in upcoming posts I will discuss current research about Fto in both humans and animals.  It is not known, for example, what Fto is actually doing in the brain, and what its normal function is.  Neither is it known exactly how it affects obesity in human populations.  Could Fto be controlling food choice?  Energy expenditure?  Or appetite and satiety?

A study by a team from London seems to suggest that part of the reason the “risk” version of Fto is linked with obesity is due to the fact that individuals carrying a copy of this gene are less responsive to satiety.  In other words, they are less able to stop eating when they are full, and may therefore be more prone to snacking during the day and eating when their immediate nutritional needs have already been met.

This study used the Child Eating Behavior Questionnaire (CEBQ) which measures two dimensions of food intake.  Satiety responsiveness is essentially concerned with how easy it is to spoil a child’s appetite – whether a child can complete a meal after having just eaten a snack and so forth.  Enjoyment of food, needless to say, is concerned mainly with the individual’s perception of eating as an enjoyable experience (independent of satisfying any immediate nutritional needs).  In this study, children carrying both copies of the “risk” version of Fto showed diminished satiety responses, and increased enjoyment of food.  This relationship persisted even when common confounds such as socioeconomic status, BMI, gender and age were controlled for.

The results of this study, as well as others like it that we will be covering in future installments of Neurobites, help us understand how genetic variations in Fto might lead to obesity.  While we have focused here on genetic correlates of obesity, it is important to remember that these genes are only able to generate obesity in an environment that properly supports excessive food intake.  The difference here may come down to a gene-environment interaction whereby the effects of our obesogenic environment are stronger in individuals carrying this genetic predisposition.  Perhaps their enhanced enjoyment of food, coupled with their impaired satiety responses creates a dangerous mix in our society, where delicious food is easy to get, and hard to avoid.

-Harry

Wardle, J., Carnell, S., Haworth, C. M. A., Farooqi, I. S., O’Rahilly, S., & Plomin, R. (2008). Obesity associated genetic variation in FTO is associated with diminished satiety. The Journal of Clinical Endocrinology and Metabolism, 93(9), 3640-3643. doi:10.1210/jc.2008-0472

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Responses

  1. Do the homozygotes for the risk gene show a similar variance in body weight compared to the hets or non-risk groups?

  2. Great article Harry! It was like I was reading straight out of Scientific American. Also, this description:
    “…that individuals carrying a copy of this gene are less responsive to satiety. In other words, they are less able to stop eating when they are full, and may therefore be more prone to snacking during the day and eating when their immediate nutritional needs have already been met,” sounds exactly like me. Uh oh I’m doomed to be a fatty!

    -DG

  3. […] far we have learned of evidence for the association between common Fto variants in humans and obesity.  We have also had a glimpse […]


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