A pregnant mom who regularly chows down on cheeseburgers probably isn't doing her baby any good; she may even predispose him to obesity, according to some studies. But when pediatrician Sheau-Fang Ng noticed that her chubby child patients tended to have not just one but two overweight parents, she began to wonder: Could dad's habits be weighing in, too? She and her colleagues have now found the first direct evidence that a father's diet, not just his genes, can increase his offspring's risk of diabetes and other diseases, at least in rats.
In a simple experiment, the researchers—based at the University of New South Wales in Sydney, Australia—fed normal male rats a diet consisting of more than 40% fat, the rodent equivalent of vending machine food. The animals quickly became obese. The rats' daughters, born from mothers of normal weight and fed a healthy diet, weren't fat, but they did show early signs of diabetes by the time they reached puberty. Not only did their insulin levels fail to rise in response to high glucose, the team reports online today in Nature, but their insulin-producing islet cells in the pancreas also expressed very different genes than do normal islet cells.
In addition, many of the daughters were underweight at birth, which, in humans, often foretells obesity later in life. Sons of fat fathers showed some signs of diabetes, too, but to a much lesser extent than their sisters. Lead author Margaret Morris believes that the sons, too, would likely develop symptoms as they age or if they were fed a high-fat diet.
The effect is "much more subtle than what studies have observed in the offspring of mothers who eat high-fat diets," says Morris. Whereas a mother's diet and hormones affect the fetus throughout pregnancy, a father's contribution is limited to conception, leading the researchers to conclude that the high-fat diet had somehow altered the male rats' sperm.
The prime suspect, says Morris, is not a genetic mutation in the sperm's DNA, but an "epigenetic" alteration in chemical tags on the DNA. These epigenetic tags help determine whether a gene is expressed, and they can be passed on to offspring. During sperm development, which is occurring constantly in the male, epigenetic marks are erased and replaced. Environmental factors such as diet may interfere with this process.
"What that means for society is that males need to be conscious of the fact that their nutrition could have impacts on their offspring before they're even conceived," says epigeneticist Michael Skinner of Washington State University, Pullman, who was not involved with the research. Men might also be wary of smoking and pesticide exposure, the harmful effects of which could also be passed down to children epigenetically, he says. "When the vast majority of disease has no correlation to any identifiable genetic abnormality, we have to stop thinking that everything is genetic."
Morris agrees. Genes alone don't explain why younger and younger people have become diabetic and obese over the past decades, she says. "Obviously, we need to do more work, but if the same phenomenon is relevant in humans, it may explain some of the recent demographic shift toward early diabetes."