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Parental Diet Affects Diabetes Risk of Children
New Rodent Studies Confirm that the Diet of Both Parents Matters
October 29, 2010
Two recent studies show that the effects of what parents do and the choices they make before having children can be passed on to the next generation. In these studies, the pups and the granddaughters of obese mice and rats were more likely to get type 2 diabetes than those of non-obese rodents.
The researchers showed that this was because of something in the DNA of the parents that was passed on. Of course, this sort of thing used to be thought of as impossible.
For a very long time the conventional wisdom has been that parents don't pass acquired traits down to their kids. If dad works out, his kids won't have bigger muscles.
For the most part, this has held true. But as scientists look harder and understand genetics better, they are starting to see exceptions to this rule. These exceptions form the basis of a growing field of biology called epigenetics.
Scientists aren't sure yet how universally important epigenetics will be. But they do know that parents' diet and their weight can lead to changes in DNA that can be passed down. And not just in rodents"ï¿œ
Obese Parents, Diabetic Offspring
In the first study, obese female mice had pups and granddaughters that were insulin resistant. Their sisters that weren't obese had unaffected pups and granddaughters.
Same genes, different methylation.
In the second study, obese male mice had insulin resistant daughters while their fit brothers did not. The researchers did not look at the sons or grandpups in this second study.
Insulin resistance is one of the first steps on the way to type 2 diabetes. So the pups and, in some cases, granddaughters of these obese mice are at a higher risk for diabetes because of what their grandparents did.
The startling finding here was that the granddaughters were insulin resistant regardless of whether their parents were obese or not. Grandma's obesity predisposed her granddaughter to diabetes.
The fact that the trait passed down two generations suggested that being obese did something to the mouse's DNA in the sperm or egg. And when scientists looked in the first study, that is just what they found.
The children and granddaughters (but not grandsons) all shared a certain change in a gene called GHSR. This gene is involved in many things including insulin regulation. Children and granddaughters of non-obese mice did not have this change.
As is usual in epigenetics, the difference the researchers found didn't change the gene itself. Instead, it changed how the gene was used.
These studies may help scientists explain some findings with obese human parents too. Obese parents are more likely to have children who are obese, have insulin resistance, and a host of other problems too.
Up until now it has been tricky to figure out exactly why this is. Are obese parents more likely to have obese kids because they pass obese genes down? Did their kids learn their parents' obese habits? Did being obese alter the DNA these parents passed down to their kids?
From the results of these studies, scientists can now see if something similar is going on in people. Whatever the result, these and other findings point to the importance of parents being fit for their children's future health. Even before they have children.
DNA has the instructions for making and running living things (including people). These instructions are written in a simple alphabet that has just four letters -- A, G, C, and T.
Cells are different because they use the same DNA differently.
Many of the differences between people come from differences in these letters. One person might have an A at one spot and another might have a G there. The A person may, for example, be at a higher risk for obesity than the G person. Any two random people will tend to have about 6 million or so of these differences or SNPs.
People inherit most of these differences from their parents but a few letters can and do change over a lifetime. But these changes tend to be random. Being obese will not cause letter changes in obesity genes that are then passed down to the next generation.
So how can being obese lead to having insulin resistant granddaughters? By changing how the existing DNA is used.
There is more to DNA than its letters. Every cell in the body has the exact same DNA even though cells can be so different (think muscle and skin cell). The differences come from which parts of the DNA get read when.
Some of the instructions for when and where to read DNA is found in the DNA itself. But some of it is actually in a layering of chemicals (called methyl groups) scattered across the DNA. It is these chemical groups that can get specifically changed through people's actions and/or environment. And it is these methyl groups that were different in the insulin resistant granddaughters.
As people live their lives, the methyl groups on their DNA shift and change depending on what they do, where they live, etc. Most of this layer of methyl groups is rearranged in the sperm and eggs -- the DNA there starts with a clean slate. Most of the effects of a person's life on his or her DNA do not appear in the next generation.
Sometimes, though, these kinds of changes can be passed down. The obesity study here shows one example. The survivors of the Dutch Hunger Winter show another. And there are undoubtedly more.
As figuring out people's DNA gets cheaper and easier, scientists will learn more and more about which methyl groups can survive rearrangements in the egg and sperm. From that they'll learn what acquired traits can be passed on to the next generation.
Cool way to talk about epigenetics using identical twins as an example.
This project was supported by the Department of Genetics, Stanford School of Medicine. Its content is solely the responsibility of the authors and does not necessarily represent the official views of Stanford University or the Department of Genetics.