Born Obese? Does your mother's diet affect your future?

Kat - If a woman is overweight and pregnant, does it mean your child is likely to be overweight?  We're joined by Professor Lucilla Poston from Kings College, London.  She's researching how foetal nutrition affects people when they're grown up.  Let's start with this thing about when you're pregnant you're eating for two.  How does a woman's diet actually affect what's going on in her developing baby?

Lucilla - Perhaps I should begin by saying it's never a good thing to eat for two.  That's what a lot of women believe - that you need to eat more.  You only need to eat a very little bit more when you're pregnant.  We are beginning to see a huge explosion in understanding of how diet in pregnancy can affect the developing child and even increase the risk of some diseases as that child grows up.  Most of the work so far has been in relation to undernutrition. People have shown that babies who are born small are more likely to develop diabetes and become obese when they grow up.  We're particularly interested, in our work in London, in the effect of over eating in pregnancy and also if a woman is already obese when she becomes pregnant.  It's been known for a long time that being obese during pregnancy is associated with lots of problems for the mum.  She may have more diabetes, more pre-eclampsia and more cases of still birth.  That indeed is a huge problem in the United Kingdom at the moment.  We do know now that the children of women who are obese tend to be obese themselves.  Well, you can say that's okay - they live in the same family and have the same genes and so on but there are some studies which suggest that there is something going on in relation to what the mother's eating or whether she's fat and in relationship with the child's obesity.  There are some very good studies that suggest it's an independent association related to genes.  Not convincingly proven yet but actually what is so interesting is that we've been looking at obesity in animals and we've been making mice and rats obese in pregnancy.  We found remarkably that the young animals grow up obese even though they're eating a normal diet.  That's got us really excited.

Kat - There's a fundamental change in their metabolism?

Lucilla - Yes and what we're seeing is they're actually eating more so they have an increase in appetite and they sit around more.  They're less active so as Professor Bloom was saying earlier it's all a relationship between what you've taken in and how much exercise you do.  These animals seem to be eating more and taking less exercise.  It's hardly surprising that they become fatter.

Kat - In my previous incarnation as a scientist I was working in the field of epigenetics, looking at how things that happened to your genes when you're developing as a foetus can affect the size that you are.  Also, the thing we used to get told about in the field was the Dutch mothers, the women who were pregnant during the war.  They had very little food and they had babies who were very small.  Then when the war was over and everyone had enough food again these small babies who'd grown into women then had small babies themselves.  It's suggested there's a change that actually happened to their genes.  Is this the same thing going on but in fat?

Lucilla - Well there is certainly evidence that if you treat animals with less dietary intake, you give them an under-nutrition diet in pregnancy, you can show categorically that some of their genes are permanently changed.  What people have been looking at is the methylation status of the promoter region of certain genes which control growth.  They are remarkably different in the offspring of animals which have been subjected to under nutrition.  On the converse side we're looking at that now in relation to obesity.  There's much less evidence so far but we're beginning to see data coming out both from our laboratory and others that there are permanent changes to the expression of some genes.  That could be due to altered methylation status.  It's very exciting.

Kat - These are the switches that switch genes on?

Lucilla - Yep.

Kat - Those sort of mechanisms, they probably act - isn't it quite early in the development?  What sort of time from the development form an egg to a foetus to a born baby are these kinds of influences of maternal weight acting?

Lucilla - We've been doing some work on preimplantation embryos.  That's before the embryo gets embedded in the womb.  We've been looking at mitochondrial activity and they're very different if the mother is obese.  This is again from animal studies.  It could suggest that very early on there's an impact of obesity.  More recently we've been looking at the post-natal period and during the suckling period and we think that's incredibly important in relation to the development of the hypothalamus of the offspring.  Professor Bloom was talking about that.  The hypothalamus is the seat of energy control and it produces lots of peptides that control appetite.  We're seeing remarkable changes in the expression of those peptides in the hypothalamus in the offspring of animals who are obese.  It may be that the suckling period is particularly important or late gestation.  Probably different periods all adding up to creating slightly different phenotype in the offspring.

Kat - And to stress this isn't just to do with the nurture, the type of household you're brought up where there's lots of food and if you're overweight it really is something that's in the genes and how they interact with the environment?

Lucilla - It's extremely difficult in human studies to tease out the contribution of genes and the contribution of the shared environment.  People are trying to do that by statistical analysis and it is very hard to prove that this is an acquired defect in terms of appetite and obesity, so that's where the animal studies come in very strongly because obviously we could use animals of exactly the same genetic background, we can control the environment and so on.  The animal studies at the moment are telling us far more than the human studies.  Some human studies are planned, including in the United Kingdom whereby we're going to intervene in obese ladies' pregnancies to try and improve diet and then we'll be looking at the genes of their children to see if the intervention has had any effect in relation to the expression of some genes relating to appetite control and so on.  We have the potential to do it.  Most of the evidence so far has been from animal studies.