Men, your sperm know how heavy you are. A new study reveals that sperm carry different chemical tags on their DNA depending on whether their owner is lean or obese. The findings suggest that men may be able to pass information about the availability of food in their environment down to their offspring, which could influence their child’s odds of being overweight.
The new data are preliminary but provocative, says Wolf Reik, who studies epigenetics at the Babraham Institute in Cambridge, U.K., but was not involved in this work. It’s the first time anyone has identified changes in these chemical tags—known as epigenetic changes—in the sperm of obese men, he says. But the subjects are few, he notes, and such studies are always complicated by genetic differences between the subjects. It is also notoriously difficult to show exactly how epigenetic changes in sperm or eggs affect development.
The observations do fit with evidence from a number of studies that have shown that parents’ body weight has long-lasting effects on offspring. Mothers who were pregnant during a 1944 famine in the Netherlands, for example, were more likely to have children—and grandchildren—prone to heart disease, diabetes, and obesity. Female mice that are underfed during pregnancy also give birth to pups that are more likely to develop diabetes—and their male offspring have epigenetic changes in their sperm. The offspring of those males are also prone to diabetes. Male rats that are overfed, when mated with healthy females, also had offspring that were prone to developing diabetes. The connections make evolutionary sense, because it could be an advantage to signal the next generation whether food is plentiful or scarce.
Romain Barrès, who studies the genetics of metabolism at the University of Copenhagen, wanted to see whether there was evidence of such epigenetic changes in human sperm. He and his colleagues collected sperm samples from 13 men who were “lean,” with a median body mass index (BMI) of 23, and 10 men who were obese, with a median BMI of 32. (A man who is 180 cm and weighs 75 kilograms has a BMI of 23. Someone of the same height with a BMI of 32 weighs 104 kilograms—229 pounds.) They then looked at various epigenetic markers in the sperm. ?
The patterns of a type of molecule that influences epigenetic inheritance, called small noncoding RNA, differed between the two groups, as did methylation patterns in the sperm DNA in the two groups, the team reports today in Cell Metabolism. Gene methylation, also called imprinting, helps determine whether a gene is turned on or off. The researchers found more than 9000 genes that were either more or less likely to be methylated depending on whether the subject was lean or obese. Many of the genes were related to brain development, appetite control, and metabolism.
The changes in genes related to brain development and function are especially intriguing, Barrès says. “Brain function is a very important variable when it comes to obesity.” He also notes that other studies have found that obese men have a higher risk of having children with autism spectrum disorder. The methylation differences between the lean and obese groups were consistent with those found in a recent study of methylation changes in sperm from fathers who had more than one child with autism spectrum disorder.
To see whether weight loss would affect sperm epigenetic markers, the researchers collected sperm samples from six men who were about to undergo gastric bypass surgery. They then collected samples a week after surgery and a year later. They found differences in DNA methylation in 1509 genes just a week after surgery, suggesting that epigenetic changes can happen quickly. “It implies that it’s very dynamic,” Barrès says. A year later, once the men’s weight had stabilized, the team found changes in 3910 genes. Roughly 40% of those genes were also found to be altered in the study comparing lean and obese men.
Gilean McVean, who studies statistical genetics at the University of Oxford University in the United Kingdom, says much stronger data are needed to make the case that nutritional signals are transmitted through epigenetics. Obese and lean men very likely have different epigenetic patterns in tissues throughout their bodies, he says, including sperm. “Whether the sperm differences have any functional consequence for children,” he wrote in an email, “is an entirely different matter.”
*Correction, 3 December, 3:37 p.m.:?The story has been updated to correct the name of the journal publishing the paper. It is Cell Metabolism, not Molecular Cell.