British culture seems to take
umbrage at the notion that genes play a role in obesity. Just a few weeks ago, a
years-old BBC Have Your Say article about the weight of
Europeans resurfaced to the 'most popular' page, bringing with it pages of vitriol
and condemnation levied at the overweight - and that was just in the highest-rated
It often seems that the media pushes
the idea that the obesity epidemic is fuelled almost entirely by our
increasingly well-fed and sedentary lives, which makes the opportunity to hear
solid evidence for the other side of the equation refreshing.
Kicking off the first in a series of
lectures in the Society's new home, the
talk started by going over what we think we know about fat. We were
reminded that while losing fat from your body can be healthy if you have too
much, it can also be unhealthy when you have too little. Your body needs fat,
of the right types, in the right amounts and in the right places, to function
But how do we know if genes are
involved in controlling our weight, or our adiposity (that is, how much fat you
have)? Well, there's a tried and tested way to do
this: get a bunch of twins, and see if the identical twins (who share all their
genes) share a trait more often than fraternal twins (who share only share half
If they do, then it's a good indication that genes influence that trait. You
can guess where this is going. That's right, identical twins are more
likely than fraternal twins to both be obese, and are likely to have similar
levels of obesity.
Then we get on to Professor
Blakemore's field of research - finding and
investigating genetic differences that play a role in adiposity. This is where we
start to see the complexity of the genetic contribution to obesity.
The simplest genetic change that can
influence obesity (or indeed anything else) is when one letter of DNA differs
between people, which we call a single nucleotide polymorphism (SNP). There are
currently at least 32 SNPs
associated with body mass index (BMI). A number of these, we were told,
lie in or near the gene FTO, which when described in mice
was originally called Fatso, due to the DNA coding sequence being so long. Needless to say, when people found out that it was linked to obesity in
humans it underwent a hasty name change.
Despite so many SNPs being found, we're still only seeing part of the picture. Having
particular obesity-associated versions of FTO was linked to an average weight
increase of three kilograms; 'I'm sorry, but I could do
that in a weekend!' Professor Blakemore joked.
These SNPs therefore appear just to influence
on which side of average-weight people end up, despite the twin studies
discussed earlier having shown strong evidence for a genetic involvement. This
discrepancy gets called the 'missing
heritability' of obesity.
There are of
course more ways for genomes to differ than by single letters. Chromosomal
deletions, where a chunk of DNA gets removed from the genome, are known to
cause various syndromes which include obesity as a symptom. Professor Blakemore's
own research group identified a case of Prader-Willi
Syndrome that was not detected by the usual diagnostic
methods, by looking for extremely
Finally, mutations in individual
genes can influence obesity, as is the case with deficiencies in the hormone leptin, or
receptor. All this work done by Professor Blakemore and others
serves to demonstrate the complexity of the genes involved in regulation of our weight.
There is a theme running through
these weight-associated genes; the vast majority are involved in the regulation
of behaviour. If you consider how common some of the variants are, and how
different combinations of them might interact, we begin to get a feel for just
where that missing heritability might be coming from.
ended with a consideration of how we can use all this genetic information. First,
we can use it to inform personalised medicine, or to guide research into new therapies.
On a different scale, we could try to moderate or overcome media stigmatisation
of obesity, by recognising that the neural circuitry which strongly influences eating
behaviour can indeed differ between individuals.
We could also increase
the use of genetic screening and counselling, to help people decide how best to
play the genetic hand they were dealt. In a sad, timely example, just two days
after this lecture a story broke of how 74
children in parts of the UK have been taken into care
in the last three years for being overweight. Who knows what underlying
genetic factors might have influenced these children's weights - shouldn't that
have come into consideration?
This was one of
the best evening lectures I have been to in a long time. I went into
this talk not knowing much about the genetics of obesity and I learnt a
lot. Professor Blakemore was an engaging, personable
speaker, who not only dealt with the scientific but the social implications of
genetic involvement in obesity. The Society filmed the event, so I suspect it
will end up online; if it does, I highly recommend you watch it.