What You Eat Controls Your Genes

The phrase is quite common utilize: "you are what you eat", a concept about which I have written many times, for example:

YOU ARE WHAT YOUR MOTHER EATS

NO STUPID YOU ARE WHAT YOU EAT!!!

So how does what we eat make us who we are? The most obvious can be observed just by looking at someone, one who eats far more calories than their body requires will eventually be over weight, or worse, obese. But this is only a small part of the effects that foods have on our bodies. The unseen effects are many with one type of effect able to be passed on to ones offspring. What we eat ultimately alters the ways in which our genes are controlled that does not involve changes to the nucleic acid sequences of our genes. This latter type of effect is referred to as epigenetics. Simple defined, epigenetics refers to phenotypes that are the result of effects "on" our genes and not by our genotype. Epigenetic modifications include both modifying nucleic acids in our DNA, the most common being methylation of the nucleotide, cytidine (C). The other type of epigenetic modification occurs to the proteins, histones, that are primarily responsible for the structure of our DNA. There are numerous different types of histone modification such as acetylation and methylation.

Metabolism refers to the extraction of energy from the food we consume and the manipulation of the elements into other substances such as proteins, fats, and carbohydrates. During human evolution we needed to modify metabolism as a result of changing environments as a means to capture, often times, limited and unstable sources of energy.

The metabolic (biochemical) reactions that take place in all cells are, for the most part, determined by the carbon sources. The information for how, when, and where to make the enzymes required for all the various metabolic processes is encoded in our genes. Adapting to changing nutritional environments involves changing the patterns of gene expression so that our cells can adjust their metabolism according to the availability of different carbon sources and other essential nutrients such as vitamins and minerals.

Given that our genetic makeup is essentially fixed it cannot be quickly changed to accommodate a changing environment and alterations in the availability of nutrients. Rapid responses are typically mediated by signaling molecules that trigger changes in transcription programs in cells. However, once the initiating stimulus is gone, the response is typically no longer occurring. Modifying the nucleotides and modifying the histone proteins that control the structure of chromatin, and therefore the expression of genes, represents the process of epigenetics.

So how exactly does the food we eat impact the epigenetic modifications that take place in our chromatin? The metabolism of numerous compounds that includes amino acids and fatty acids yields a compound called acetic acid. Within our cells this compound is attached to the vitamin-derived compound, coenzyme A (CoA), forming acetyl-CoA. Acetyl-CoA is used by histone acetyltransferases (HAT) for the acetylation of histones, a form of epigenetic modification. When histones are acetylated the structure of chromatin is more open and expression of genes in that area of the chromatin are more likely to be expressed, conversely deacetylation of histones reduces gene expression. The amino acid methionine is used to make the universal methyl donor S-adenosylmethionine (SAM; also written AdoMet). The synthesis of SAM requires not only methionine, but also energy (ATP), and the vitamins folate and B12 (cobalamin). Lysine methyltransferases (KMT) and DNA methyltransferases (DNMT) utilize SAM to methylate histones and DNA, respectively both of which represent forms of epigenetic modification.

Additional histone modifications, that are epigenetic, include many forms of acylation. These acylations include beta-hydroxybutyrylation, succinylation, propionylation, crotonylation, and butyrylation to mention only those modifications that have been more heavily characterized. Beta-hydroxybutyrate is called a ketone body and it is derived, predominantly, from the metabolism of fatty acids. Succinyl-CoA is an intermediate in a metabolic pathway called the TCA cycle or the Krebs cycle. The TCA cycle is a major pathway for the metabolism of amino acids, carbohydrates, and fatty acids. Propionyl-CoA is a product of the metabolism of certain types of fatty acids as well as several amino acids. Crotonyl-CoA is primarily a product of the metabolism of the amino acids tryptophan and lysine. Butyryl-CoA is generated via mitochondrial β-oxidation of fatty acids and also via mitochondrial fatty acid synthesis. Butyrate is one of the major short-chain fatty acids (SCFA) derived from the action of gut microbiota.

So how then does eating ultimately control gene expression? The tight coupling of epigenetic processes to the cellular metabolism via the availability of cofactors also means that the epigenome and thereby the gene expression programs of cells and organisms respond

to metabolic changes and perturbations. For example, both long-term and drastic short-term imbalances at the level of methionine, folate, or B12 can have effects on global and gene-specific DNA methylation patterns which, in turn, can lead to long-lasting changes in gene expression patterns that can affect an individual’s health. In addition, these types of effects have been shown to be transgenerational, meaning they can be passed on to one's offspring.

So clearly what we eat and how often we eat exerts profound effects on our genetic material. These effects can be beneficial and they can be harmful, with the latter being associated with excess intake of the metabolic intermediates of the epigenetic modifiers.