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You are what your mother ate

In the last 20 years we have observed a vast increase in the incidence of obesity and its myriad of associated diseases, but we lack a full understanding of what has caused this. There are many players that come together to make up 'team obesity', some having greater impact on the epidemic than others. The superstar strikers are definitely the changes to diet and lifestyle observed in recent years. On the substitutes' bench are genetic mutations; those identified mainly alter feeding habits and cause severe obesity. These are thankfully very rare. Scientists are continually searching for more players in the team who may then be targeted in a therapeutic manner. A strong candidate that has drawn attention recently is foetal programming.

The theory of foetal programming suggests that the developmental environment can lead to long-term changes in an organism. The German evolutionary biologist August Weismann nicely illustrated this back in the 19th century. He noticed two distinct forms of the butterfly Pieris napi; butterflies that developed in the winter had dark colourings while those developing in the summer had a lighter pattern. This is a simple but striking example of how the developmental environment, in this case temperature, can alter the message encoded in the genes.

This idea has since been extended to humans and is now suggested to play a role in obesity. This concept first came about from observations made following the Dutch Hunger Winter of 1944. Women who were pregnant during this harsh winter had babies of low birth weight. Although 'starved' during their development, obesity, high blood pressure and heart disease were found at higher prevalence once the babies reached adulthood. This remained true when factors such as current diet and lifestyle were taken into consideration. Importantly, these changes could not be due to genetics, as tens of thousands of people of different backgrounds were affected.   

Could under-nutrition during foetal development be a cause for obesity in later life? This could potentially be the case in developing countries, although it is unlikely to play a role in more developed nations, where over-nutrition seems to be the biggest problem.

In the UK for example, over 20% of women of childbearing age are considered obese, a figure which has considerably increased in recent years. It is now well established that these women have more complications during labour and that their newborns are more likely to need time in intensive care following birth.

Could gestational over-nutrition also lead to an increased risk of obesity and diabetes in the offspring? As the obesity epidemic is a relatively new phenomenon, studies addressing this question are, like the children affected, in their infancy. However, preliminary results tend to point in this direction.

Due to the lack of human data available, animal models have been developed to give us insights into the potential problems of maternal obesity. In many research centres, including here at the University of Edinburgh, over-nutrition during pregnancy is being modelled in pregnant rodents fed diets rich in fat and sugar. Although it would seem likely that babies from these mothers would be heavier, increased birth weights are not consistently seen. However, by the time these babies are three months old, there is already evidence of extra fat deposition, altered metabolism of ingested fat and changes in insulin sensitivity, which in the long term can lead to type-2 diabetes. Worryingly, these phenotypes are seen even when offspring are fed a standard balanced diet, suggesting the effects of the maternal diet cannot be easily reversed by a healthy lifestyle. Unsurprisingly, the changes in metabolism mentioned are further exacerbated by feeding offspring a high-calorie diet. This is important as it would seem logical that children growing up with obese parents are more likely to be fed an unbalanced diet and build unhealthy eating habits themselves.

Differences between humans and rodents aside, this research certainly gives us an insight into how conditions during pregnancy may 'programme' the future of a child, though the exact mechanisms that control this continue to elude scientists. Uncovering these mechanisms is now a strong focus of research in animal models of foetal programming, but until they are found it seems a vicious cycle: children born to obese mothers are more likely to become obese themselves, as are their children, and their children's children.

It's clear that the players in team obesity are increasing in number as we add foetal programming to the lineup. Whilst I would never deny 'you are what you eat', I think it’s also worth considering that you might be better or worse off because of what your mother ate.

Rachel Dakin is a PhD student in the Centre for Cardiovascular Science


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