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4 December 2014

A new paper shows evidence that what fathers eat can affect susceptibility to obesity in future generations


The idea that changes in the body accumulated during the lifetime of that individual could be passed on to their children and children's children has been largely discarded. In recent years a few studies have hinted that in fact, the diet of parents could affect physical features in future generations, but quite how this happens has remained obscure.

In a paper published in Cell today researchers from the IMPPC, working with groups in Germany, Sweden and Portugal have published new evidence that demonstrates a mechanism by which feeding habits in fathers can affect whether their offspring are prone to become obese or not. They observed that
male flies fed a diet that is abundant in sugar produced offspring that are more susceptible to obesity during adulthood. Males are used in these studies because males only pass genetic material to the offspring in sperm, whereas for females other substances in the egg cell, or conditions during pregnancy will also have an effect, which makes it difficult to see purely inherited effects. The experiments are carried out in fruit flies (Drosophila melanogaster) because so much is known about their genetic mechanisms and many generations can be bred in a very short time.

The Cell paper describes the mechanism, called Intergenerational metabolic reprogramming (IGMR), by which males who were fed more sugar produced offspring more prone to obesity than males who were fed less sugar. IGMR has two effects on the next generation; individuals offered high-sugar content food are heavier with a tendency to accumulate fat, but they also have a tendency to eat more. The scientists also tested whether this change could be reversed in sperm before conception and found that paternal stress, caused by exposure to high temperature, did destroy the effect of IGMR.

To study the mechanism, scientist next looked at which genes were switched on and off in obese-prone young flies from fathers fed a lot of sugar. Using sophisticated computational techniques the IMPPC researchers revealed the activation of genes known to affect energy metabolism and also chromatin control. Chromatin is the combination of genetic material and the proteins in which it is packed. Changes in the packaging open and close the chain containing the genetic code and allow genes to be activated or kept quiet. In this case they found that whether a gene was involved in the IGMR affect depended on the state of the chromatin it was in. Sugar in diet was found to loosen chromatin packaging and allow genes within it to become switched on in early embryos. These changes are stable in the offspring and stay with them for life.

Obviously such experiments cannot be carried out in people but the researchers looked at data from previous studies of obesity, two carried out on mice and three more on people. They found that chromatin packaging also predicts obesity in these species meaning that it is possible that the same effect takes place in fruit flies, mice and humans.

These results give a fascinating insight into how evolution may have tailored populations to cover their bets and produce individuals that are different. Circadian or other fluctuations in parental food intake would lead to individuals who are equipped to fare better than others in different conditions.

In terms of humans, obesity is a major problem in the developed world and a huge financial burden to health systems. Although this work cannot be said to have direct implications for people, it does give a fascinating glimpse of how research in the future might find out more about its causes.
 

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