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Epigenetics and DNA

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English: nutrigenomics, flow chart, diet, gene...

English: nutrigenomics, flow chart, diet, genes, disease (Photo credit: Wikipedia)

Why is what pregnant women eat before, during, and after pregnancy so important to the development of the unborn embryo/fetus? Recent evidence indicates that environmental factors may play an important role during early life development with potential long-term effects on health in later life. How do these factors influence the genes we already have in place?

There is an emerging concept called “early programming” that simply states that the fetus adapts to its existing environment when it is less than optimal, e.g., when the diet is lacking in essential nutrients for its development. This results in suboptimal development with long-term implications leading to increased risk of diseases such as heart disease, obesity, metabolic syndrome, glucose intolerance, or insulin resistance in adulthood. We now know that genes are switched on and off leading to functional physiological differences between individuals.

How are our genes modified? The most common alteration is a change in the nucleotide called single nucleotide (polymorphism (SNPs). For example, a SNP may replace the nucleotide C (cytosine) with the nucleotide T (thymine) in a certain position in a person’s DNA. This change is permanent.

Another way is through epigenetics. Epigenetics is the study of any change to our DNA that modulates a gene’s activity by turning them on and off. They result from exposure to the world – everything we eat, drink, breathe, feel and do, i.e., our environment. They are temporary so it is possible to correct our previous behaviors such as smoking cessation, exercising more or improving our diets to provide a more favorable health status.

The nutrients we extract from food enter metabolic pathways where they are formed into the molecules the body can use. One such pathway is responsible for making methyl groups. The methyl groups are epigenetic tags that attach to our DNA to modulate its activity to silence genes. Another epigenetic process is the production of acetyl groups (acetylation) to DNA histones that enhances the expression of the gene. So one pathway “turns off” the gene and the other “turns it on.” These modifications are particularly important during development of the fetus. Some modifications continue to have an effect into adulthood.

Methyl-Group

Methyl-Group (Photo credit: Wikipedia)

Nutrients like folic acid, B vitamins, and others are key nutrients in these processes. Diets of pregnant women high in these nutrients can rapidly alter gene expression, especially during early development when the epigenome is first being established.

What foods are rich in epigenetic nutrients? The list may sound familiar.

Leafy vegetables, seeds, nuts, liver, meats, whole grains, egg yolks, red wine, soy, broccoli and garlic provide methyl groups or are involved in acetylation. For example, sulphoraphane in broccoli increases acetylation turning on anti-cancer genes. Butyrate (a compound produced in the intestine when dietary fiber is fermented) turns on protective genes. Folic acid, vitamin B6  and vitamin B12 provide methyl groups.

Animal studies have shown that a diet with too little methyl-donating folate or choline before or just after birth causes certain regions of the genome to be under-methylated for life. This can produce permanent changes.

For adults too, a methyl-deficient diet leads to a decrease in DNA methylation, but the changes are reversible when methyl is added back to diet. So changes in the diet can create a healthier environment to help to prevent chronic diseases, but the behaviors need to change.

To fully illustrate the epigenetic process, one must tell the story of the agouti gene. All mammals have a gene called agouti. When a mouse’s agouti gene is completely unmethylated, its coat is yellow and has a high risk for obesity.  When the agouti gene is methylated (as it is in normal mice), the coat color is brown,  the mouse has a normal weight and less disease risk.   The mice are genetically identical but the fat yellow mice are different because they have an epigenetic “mutation.” in this case the presence or absence of methyl groups in its DNA.

issue28epigenetics12_l

In a study pregnant yellow mice were  fed a  a methyl-rich diet;  most of her pups were brown and stayed healthy for life. These results show that the environment in the womb influences adult health.

The Emerging Field of Nutrigenomics

Possibly in the future of diet and nutrition there may come a time when we can use the concept of nutrigenomics to better understand why one person reacts to a particular dietary intervention more than another does. This may also explain why nutrition research is so erratic with studies reporting conflicting results and conclusions.  In the future, there is the potential for genetic testing that will result in genetic profiles that can aid in forming personalized diets and fitness plans, which will help minimize risks for disease.

We all know that a nutrient-rich diet is healthy and it is becoming increasingly clear that it  is not only what we eat in a lifetime but what our parents ate before our conception that can make a difference in our health status in adulthood.

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