Research has shown that when fathers consume a diet high in fat or low in protein it can increase the risk of metabolic disorders like diabetes in their offspring once they reach adulthood. Scientists have now learned more about the mechanisms underlying that phenomenon, which are thought to be connected to epigenetics. While our genome typically does not change much through life, chemical groups or epigenetic tags can be added to or removed from genes, impacting how genes are expressed. Studies have shown that some epigenetic tags are heritable.
Reporting in Molecular Cell, a research team led by Keisuke Yoshida and Shunsuke Ishii at the RIKEN Cluster for Pioneering Research used a mouse model to identify a protein that is critical to the heritability of epigenetic tags. The molecule is called ATF7 and it is a transcription factor, which is a molecule that can impact how genes are expressed.
In this study, the researchers split mice of both genders into two groups, one of which was fed a typical diet while the other got a diet low in protein. These groups were then mated. The scientists then looked at gene expression in adult male mice that were offspring of male mice fed either diet. Hundreds of genes that are active in the liver were found to be expressed differently in offspring derived from the two groups. This work was repeated using male mice that were engineered to lack a copy of the ATF7 gene. This time, the offspring did not show the same changes in liver gene expression between the groups (that were offspring of males fed either a normal diet or low-protein diet).
This work has suggested that the diet of a male mouse can impact the health of its offspring. The same effect was not seen in the offspring of females that were pregnant. Thus, the researchers concluded that epigenetic changes in sperm are probably causing these changes, and that ATF7 is vital to the process.
These findings led the scientists to look for genes controlled by ATF7 in sperm cells, revealing genes that play a role in fat metabolism and the production of cholesterol. When expectant fathers were put on a low protein diet, the ATF7 transcription factor stopped working to turn those genes off as it would normally, and instead, the genes became active.
"The most surprising and exciting discovery was that the epigenetic change induced by paternal low protein diet is maintained in mature sperm during spermatogenesis and transmitted to the next generation," Ishii said.
This work can help explain why poor diets in fathers can contribute to health problems like diabetes in their adult children. It may also help create a way to measure the risk posed to those children by assessing the epigenetic tags in sperm cells.
"We hope that people, especially those who have poor nutrition by choice, will pay more attention to their diet when planning for the next generation. Our results indicate that diets with more protein and less fat are healthier not just for everyone's own body, but also for sperm and the health of potential children."
Learn more about how diet-induced epigenetic changes in parents can influence the health of their offspring from the videos.
Sources: AAAS/Eurekalert! via RIKEN, Molecular Cell