WHAT’S BRED IN THE BONE
How the effects of a poor diet can last for generations,
Obesity is on the rise globally, driven by the relative ease of obtaining processed, high-fat foods, according a new study in Nature. As a result more adults are obese than underweight, say the authors.
And obesity, along with its health risks, may be inheritable, according to the emerging field of epigenetics. Researchers are uncovering evidence suggesting that the impacts of obesity predispose children and grandchildren to diseases like diabetes and heart disease before they’re born.
Epigenetics is the process through which the environment influences our DNA. Substances in the air we breathe, the water we drink, the food we eat and our own hormones enter cells and affect DNA by epigenetic regulation. The most well studied way for DNA to be regulated by epigenetics is through the addition of a chemical tag on top of DNA.
Such epigenetic regulation can determine whether a gene is active or inactive. For example, epigenetic tagging will tell the cellular machinery to use or skip over a particular gene. If your whole genome can be likened to a Spotify library, then the selection of particular genes by epigenetic regulation is similar to making a special playlist from the whole library. Epigenetic regulation ensures that the gene for blue eyes is turned on in eyes and not turned on in the heart; each organ has its own gene playlist.
Researchers are learning that normal epigenetic regulation is disrupted in certain diseases like obesity and diabetes. And, although epigenetics research is considered a young field, it has attracted international attention due to its potential to help understand and control health issues of global importance.
Large-scale international research teams have rallied to gather and analyze samples from groups of people with a particular disease or who have been exposed to environmental toxins.
The International Human Epigenome Consortium is co-ordinating research teams to study the epigenome of 1,000 people. Its goal is to understand how epigenetic regulation has moulded human populations across generations and how disruption of such regulation may lead to disease.
Canada is one of the partners in this consortium, along with the U.S., Germany, Hong Kong, Japan, Singapore and South Korea.
Epigenetics research is starting to shed light on the ways in which diet — specifically the increased consumption of processed foods with high sugar and fat content — can promote Type 2 diabetes across generations.
High-fat diets are linked to disruptions in the epigenetic regulation of genes as summarized in a review article published in the journal Cell Metabolism, on May 7. Many genes, some of which are known to be important for regulating blood glucose levels or appetite, were abnormally regulated by epigenetics and switched on in obese subjects and people with Type 2 diabetes. The researchers think these epigenetic abnormalities may forecast the future risk for type 2 diabetes. But the research is not there yet.
Encouragingly, some studies suggest it is possible to wipe clean such abnormal epigenetic regulation, by exercise for example. The epigenetic abnormalities linked to Type 2 diabetes could be reversed by exercise in men who had previously been inactive.
Diet and lifestyle induced changes in epigenetic regulation may also be passed on to children. Studies of larger populations are required, but as reviewed in the journal, the Lancet, Diabetes and Endocrinology, on May 22, there is emerging data suggesting that obesity and high blood glucose in mothers increases the risk of obesity and Type 2 diabetes in their offspring through epigenetic changes caused by high glucose levels in the uterus. There is also the possibility that obesity in the father and epigenetic changes in their sperm can increase the future risk of disease in their children.
The developing embryo is controlled not only by maternal influences, but also epigenetic regulation from the father’s sperm. Qi Chen and his colleagues from the division of biomedical sciences, UC Riverside School of Medicine, found that high-fat diets can affect sperm epigenetics and increase the susceptibility of the fathers’ children to Type 2 diabetes.
Dr. Tessa Roseboom (University of Amsterdam) discussed the “Dutch famine birth cohort” at a recent meeting of the Canadian Society for Developmental Origins of Health and Disease (DOHaD). She talked about the grandchildren of Dutch women who were subjected to starvation during the Second World War. The research is ongoing, but the results suggested that the children of children who were born while the grandparent was starved showed higher susceptibility to disease than the children of children who were born when that grandparent had enough food to eat.
Epigenetics research not only has the potential to reveal how nutrition and exercise choices can affect the risk for disease, but it may also explain the health effects of trauma and industrial pollution.
The International Society for Developmental Origins or Health and Disease contains groups that focus exclusively on studying the impact of environmental toxins such as pesticides and heavy metals, like arsenic and mercury, on epigenetic regulation and the health of fetuses, exposed in utero.
Some investigations, in progress, even suggest that if toxic factors enter reproductive cells of the fetus, like eggs or sperm, to cause epigenetic changes, the detrimental health effects of pollutants could be passed from the person initially exposed to their future grandchildren.
The pesticide DDT is sprayed to kill malaria-carrying mosquitos in Africa and then travels by ocean currents to the Canadian Arctic where it can accumulate. Dr. Janice Bailey of Universite Laval is planning to study the effects of DDT in the Arctic on epigenetic regulation and the health of Inuit communities. She is also studying whether dietary folate, a B vitamin, can prevent the epigenetic effects of pesticide-contaminated food consumed by fathers from being passed on to their offspring.
Dr. Takashi Yorifuji of Okayama and Dr. Philippe Grandjean of Harvard University are analyzing the effect of arsenic poisoning on epigenetics in bottle-fed infants in Japan.
“In 1955, we had severe arsenic poisoning due to contaminated milk powder,” Yorifuji says. This incident occurred in the western part of Japan, and more than 100 died.
The other victims were found to have neuropsychological problems in their teenage years and as adults. The researchers are trying to find out if the arsenic disrupted epigenetic regulation.
Researchers are still investigating the links between epigenetic dysfunction and disease development and are optimistic that by validating these links, they will expand the tool kits for disease diagnosis and possibly disease prevention.
The mandate of the Broad Institute’s Epigenomics Program at MIT and Harvard is to “open up new diagnostic and therapeutic opportunities” according to its director, Dr. Brad Bernstein. To date, abnormal epigenetic regulation has been implicated in cancer, autism and Alzheimer’s, with drugs targeting such regulation already finding approval as therapies for cancer.
Results suggested that the children of children who were born while the grandparent was starved showed higher susceptibility to disease