Paternal Diet Can Affect Genes and Health of Offspring, Research Suggests

Dec. 23, 2010

AUSTIN, Texas — Environmental influences experienced by a father can be passed down to the next generation, "reprogramming" how genes function in offspring, scientists at The University of Texas at Austin and the University of Massachusetts Medical School (UMMS) have discovered.

A new study published this week in Cell shows environmental cues — in this case, diet — influence genes in mammals from one generation to the next, evidence that until now has been sparse.

These insights, coupled with previous human epidemiological studies, suggest paternal environmental effects may play a more important role in complex diseases such as diabetes and heart disease than previously believed.

"Knowing what your parents were doing before you were conceived is turning out to be important in determining what disease risk factors you may be carrying," said Oliver Rando, associate professor of biochemistry and molecular pharmacology at UMMS and coauthor of the study with Hans Hofmann, associate professor of integrative biology at The University of Texas at Austin.

The study details how paternal diet can increase production of cholesterol synthesis genes in first-generation offspring.

The human genome is often described as the set of instructions that govern the development and functioning of life. Most contemporary genetic research focuses on understanding and cataloging how mutations and changes to our DNA — the basis of those "instructions" — cause disease and affect health.

A number of recent studies, however, have begun to draw attention to the role epigenetic inheritance — inherited changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence — may play in a host of illnesses.

"A major and under-appreciated aspect of what is transmitted from parent to child is ancestral environment," said Rando. "Our findings suggest that there are many ways that parents can 'tell' their children about what they 'saw.'"

To test their hypothesis that environmental influences experienced by the father can be passed down to the next generation in the form of changed epigenetic information, Rando, Hofmann and colleagues fed different diets to two groups of male mice. The first group received a standard diet, while the second received a low-protein diet. To control for maternal influences, all females were fed the same, standard diet. The researchers observed that offspring of the mice fed the low-protein diet exhibited a marked increase in the genes responsible for lipid and cholesterol synthesis in comparison to offspring of the control group fed the standard diet.

These observations are consistent with epidemiological data from two well-known human studies suggesting that parental diet has an effect on the health of offspring.

One of these studies, called the Överkalix Cohort Study, conducted among residents of an isolated community in the far northeast of Sweden, found that poor diet during the paternal grandfather's adolescence increased the risk of diabetes, obesity and cardiovascular disease in second-generation offspring. However, because these studies are retrospective and involve dynamic populations, they are unable to completely account for all social and economic variables.

"Our study begins to rule out the possibility that social and economic factors, or differences in the DNA sequence, may be contributing to what we're seeing," said Rando. "It strongly implicates epigenetic inheritance as a contributing factor to changes in gene function."

The results also have implications for our understanding of evolutionary processes, Hofmann said.

"It has increasingly become clear in recent years that mothers can endow their offspring with information about the environment, for instance via early experience and maternal factors, and thus make them possibly better adapted to environmental change," said Hofmann. "Our results show that offspring can inherit such acquired characters even from a parent they have never directly interacted with, which provides a novel mechanism through which natural selection could act in the course of evolution."

Such a process was first proposed by the early evolutionist Jean-Baptiste Lamarck, but then dismissed by 20th century biologists when genetic evidence seemed to provide a sufficient explanation.

Taken together, these studies suggest a better understanding of the environment experienced by our parents, such as diet, may be a useful clinical tool for assessing disease risk for illnesses, such as diabetes or heart disease.

"We often look at a patient's behavior and their genes to assess risk," said Rando. "If the patient smokes, they are going to be at an increased risk for cancer. If the family has a long history of heart disease, they might carry a gene that makes them more susceptible to heart disease. But we're more than just our genes and our behavior. Knowing what environmental factors your parents experienced is also important."

The next step for the scientists is to explore how and why this genetic reprogramming is being transmitted from generation to generation.

"We don't know why these genes are being reprogrammed or how, precisely, that information is being passed down to the next generation," said Rando. "It's consistent with the idea that when parents go hungry, it's best for offspring to hoard calories. However, it's not clear if these changes are advantageous in the context of a low-protein diet."

For more information, contact: Lee Clippard, Lady Bird Johnson Wildflower Center, 512-232-0104; Hans Hofmann, associate professor of integrative biology, 512-475-6754; Jim Fessenden, UMMS Communications, 508-856-2000.

5 Comments to "Paternal Diet Can Affect Genes and Health of Offspring, Research Suggests"

1.  Vicki Chase, RN said on Jan. 6, 2011

Hi, I am the Director of the Heart Health Institute in No. CA. We are very interested in leading edge discoveries such as yours to assist our clients in understanding their potential for cardiovascular disease. This is fascinating ! Thanks and please keep me updated. Thank you. Vicki

2.  Judith Gatchell said on Jan. 6, 2011

This is fascinating information. Is anyone out there looking at paternal alcohol consumption before conception for possible effects on offspring? I know research was conducted in the 1980s at UT about brain cell damage caused by maternal alcohol consumption during pregnancy, but I haven't heard much about it since then.

3.  Nick Barsotti said on Jan. 6, 2011

Very interesting. After just finishing The China Study my first questions are: What was the source of protein? Animal or Plants? If it was a mix, what was the ratio? How highly refined was the protein? or was the protein in a natural state? This article does not give enough information about the details of the experiment to say a low protein diet is bad. The article does not even say how few calories from protein the diet contained. Still very interesting.

4.  Enedelia Obregon said on Jan. 7, 2011

If this is so Alejandro's offspring will be super healthy.

5.  Natalie Zimmerman said on Jan. 18, 2011

I wouldn't really call epigenetics a confirmation of Lamark's ideas. Lamark believed that giraffs had long necks because generation after generation stretched their necks reaching for foliage and then transferred this trait of an elongated neck to their offspring. Epigentics deals with differential expression of genes in the genome, not newly acquired genes. The genes may manifest themselves in a new trait, but are they permanent? This is not really Lamarkian and serves to confuse biology students. It is an important point.