by Claudia Guezzou Cuervas-Mons

Nature vs Nutrition - the metabolic engine that sustains each of us is closely tied to epigenetic regulation and nutrient intake. Homeostatic bliss arises from the finely tuned balance of intricate metabolic pathways in our cells. What we eat directly affects the chemistry of our bodies and epigenetic control of metabolism and health. Changes to epigenetic regulation of metabolism can lead to unhealthy states, so what can we eat to help maintain that balance?

Providing our bodies with adequate nutrients is like putting the right oil the engine to keep our metabolism running smoothly. Equally, depriving our bodies of essential nutrients plays havoc with our metabolism. We can handle temporary deficiencies, we have backups and ways of counterbalancing, but sustained periods deficiencies can lead to problems. Prolonged deficiencies lead to lasting changes that appear after our internal metabolism loses sync and becomes dysfunctional.

The relationship between our metabolism and epigenome is bidirectional, both affecting each other. Metabolites derived from our food, including Acetyl-CoA, NAD+, and S-adenosylmethionine - a key methyl group donor in the brain, drive epigenetic machinery that shapes the dynamic 3D structure of our DNA called chromatin.

Some metabolites affect how tightly chromatin is packed. The less compact it becomes, the more exposed our DNA to transcription enzymes turning dormant genetic code into active RNA and protein. One such example is acetyl-CoA, which is mainly derived from fats and carbohydrates. Acetyl-CoA levels are well known to be closely linked to the regulation of the TCA cycle and mitochondrial activity. This metabolite closely regulates epigenetic tags such as histone tail acetylation, subsequently inducing activation or deactivation of genes related to growth depending on nutrient availability thanks to altered chromatin availability.

Polyphenols, compounds highly found in fruits, vegetables, chocolate, extra virgin oil, and wine, have numerous health benefits. They have anti-inflammatory, antimicrobial, antioxidant, and antitumorigenic properties. In an animal study published in Nature, researchers found that these compounds epigenetically induced stress resilience by promoting brain plasticity and reducing peripheral inflammation. They showed that epigenetic alterations including DNA methylation and histone modification from polyphenols triggered a reduction in depressive-like states.

Vitamin C and blueberries are packed with antioxidants which are believed to be protective against a number of diseases like cancer. They can exert their properties by means of epigenetic alterations, inhibiting the addition of epigenetic tags on specific genes including a key epigenetic enzyme DNA methyltransferase 1 (DNMT1). The result is enhanced protection of our DNA from damaging reactive oxygen species (ROS).

Another compound that has proven beneficial against environmental pollutants among others, is vitamin B. Recent research carried out in a multi collaborative platform led by Columbia University tested the effects that pollution exposure has in our epigenome and whether it could be prevented by vitamin B supplementation. Encouraging results suggested that folic acid, vitamin B6 and B12 conferred some protection against epigenetic changes caused by air pollution linked to chronic illnesses.

Yet another important player in the epigenome and metabolism interactions is our gut, which not only has a close connection with our brain but also to our epigenome. How our gut interacts with metabolites is a key determinant to how metabolites are processed and what reactions unfold. This is in part predetermined by our microbiome composition, which is highly affected by our diet. Processed foods and high sugar intake restrain our gut biome’s capacity of producing beneficial metabolites and in turn disturb the normal functioning of our epigenome.

In a similar fashion our microbiome also has a role in controlling our circadian clocks through producing metabolites that alter our epigenetic machinery. One specific circadian clock transcription factor - a protein that regulate the rate at which our genes are transcribed from DNA to RNA - has been linked to lipid metabolism and body composition. This circadian transcription factor, NFIL3, controls fat storage and has been shown to be closely regulated by our microbiome.

Our circadian rhythms are closely tuned in an interplay between epigenetics and metabolism. Our metabolism is regulated by our circadian clock which in turn is overseen by our epigenome. A key metabolite to our internal processes NAD+ is finely tuned by our internal rhythms. This means that the epigenetic alterations to induce more or less production of NAD+ are highly dependant on our internal clock oscillations as well as by our environmental needs. This complex landscape allows our organism to quickly adapt to our changing needs and states.

Epigenetics is a central player in regulating countless biological processes. The crosstalk epigenetics and metabolism is a hot target for cancer therapeutics. A number of drugs targeting epigenetic machinery mainly in cancer have recently been FDA approved. But in our daily lives the more we know about the way in which environmental factors affect our metabolism the more in control we are. This allows us to adjust to our internal needs; tailoring our nutrient intake, reducing exposure to pollutants, exercising regularly, or being mindful and avoiding stressors. As Germans would say “Man ist, was man isst.” You are what you eat!.