Mice on a fatty diet have larger grandchildren. Credit: Punchstock

You are what you eat, and so are your progeny and, perhaps, your progeny's progeny — at least, if you're a mouse.

According to research presented at the Society for Neuroscience's 38th annual meeting in Washington DC held from 15–19 November, mice fed on a high-fat diet throughout their pregnancies and suckling had offspring that were larger than normal — a trait that was also passed on to their offspring's offspring.

It is the first time that a gestating mother's diet has been shown to confer this trait on to two consecutive generations.

Long-term impact

The work is part of a larger study being conducted by neuroscientist Tracy Bale and her colleagues at the University of Pennsylvania in Philadelphia. "We wanted to know if the current increase in rates of obesity we are seeing all over the United States could have a longer-term impact," says Bale.

The mice descended from mothers on the high-fat diet were about 20% heavier than those descended from mothers kept on normal food. They were not much fatter, but they were significantly longer. They also tended to overeat, whether or not they themselves were on a high-fat or normal diet. And they were insulin-insensitive, a feature of diabetes that frequently leads to obesity.

Their own offspring — the second generation after the mothers on a fatty diet — did not overeat, but were large and insulin-insensitive. These traits were not just inherited through the female line: male pups born to mothers on a high-fat diet also transmitted them to their own offspring.

Biochemical modifications

The scientists wanted to know which genes were involved in passing on these traits. When they looked at the brains of these mice, they found epigenetic changes in the hypothalamus, a brain area involved in the control of feeding behaviour. Epigenetic changes — biochemical modifications (such as methylation) that affect the functioning of DNA without altering its nucleotide sequence — can be induced by environmental factors and can be inherited. The team is now searching for the specific genes whose methylation state is changed in these mice.

The mice in the experiment did not get fat, probably because mice do not usually have this tendency. But, in similar circumstances, humans would feel the effects, because overeating predisposes people to obesity, says Bale. If people inherit both a tendency to overeat and insulin insensitivity, then the cycle of pathological obesity will be hard to break, she says.

If the genes involved in transmitting the tendency towards obesity are identified, "then at least we can be encouraged to make decisions conducive to our health — and that of our children, and our children's children," says Bale.

Neuroscientist Li-Huei Tsai, of the the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology in Cambridge, chaired the session in which Bale's work was presented. "Epigenetic modification of the brain, so that environmental factors can change behaviour and well-being in a heritable way, is one of the major recent advances in brain research over the last decade," says Tsai.