The Unknown Link: Epigenetics, Metabolism, and Nutrition

Introduction

According to the Centers for Disease Control (Kochanek et al., 2011), about 600,000 people die of heart disease in the United States every year—that is one in every four deaths. The causes of heart disease are mainly related to nutritional and genetic factors. Many people have a genetic predisposition toward developing cardiovascular diseases. As a result, they think that making small changes to their daily lifestyle, specifically nutrition-based ones, will not help. However, epigenetics tells us something different. Not only are we passing our DNA to our children, but we are also affecting how much of that DNA will be expressed. We can make modifications in our daily lives that affect the DNA we pass on to future generations. Epigenetic modifications are heritable and may be reversible, but they do not actually change the DNA sequence itself; rather, the epigenome decides how much or whether some genes are expressed, based on our life experiences. Furthermore, there is a connection between epigenetics and metabolism that has not yet been fully explored, and I believe this relation is deeply rooted in nutrition. In this paper, I will first introduce the topic of epigenetics and the issue of obesity in America, and then describe a plan to help combat obesity, using prior research as evidence. Through this research, I want others to know that our genes do not have total control over our bodies.

Epigenetics encompasses a wide variety of topics, but in this paper, I will talk about it within the context of metabolism. I will discuss possible future research into the connection that exists between epigenetics, metabolism, and nutrition. With this knowledge, we could determine the effects of specific foods on our metabolism and possibly how to manipulate metabolic processes epigenetically. If we could develop drugs that can increase metabolic rates, they could act as a supplement for people who have tried changing their diets, but have given up after seeing no results, which sometimes occurs due to their genetic predisposition towards obesity and slow metabolism. If people were better educated about the impact that changing their diets could have to reduce their chances of developing diseases like cancer or diabetes and to help future generations by boosting their metabolic rates, more people would be willing to change their lifestyles. Although scientists are currently working on this issue, my research will pull together the pieces of information published in recent papers and further develop the connection that exists between nutrition, epigenetics, and metabolism through suggestions for original laboratory research that is aimed specifically at finding this relation at the molecular level. If we were to implement specific dietary changes to our daily lives based on this research and combine it with a supplementary, metabolic-rate-stabilizing drug and regular exercise, we could make a lasting impact that would not only improve our lives but also those of future generations, all while combating obesity.

What is epigenetics?

Epigenetics is the study of alterations in gene activity that does not change the DNA itself but can affect the way it is read and can be passed on to at least one successive generation. For example, in the 1980s, Dr. Lars Olov Bygren conducted research on the effects of famine and feast years on children growing up in Norrbotten, Sweden in the 1800s. This area was isolated, and consequently there were years with no harvest yield, which led to famine. On the other hand, there were some years during which crops were abundant, which led to a few seasons of heavy eating. Dr. Bygren studied people who experienced both famine and abundance, and their children and grandchildren. He found that the children who experienced these rare, abundant periods produced children and grandchildren who lived shorter lives, dying an average of six years earlier than the grandchildren of those who only experienced famine (Bygren et al., 2014). This phenomenon can be explained by epigenetics.

Epigenetics can affect the way our DNA is read and can be passed on to the next generation. All of our cells have coding information in the form of DNA, but our genes alone do not know what to do without direction. That is why we have these carbon-hydrogen compounds called methyl groups that bind to our DNA. Methyl groups bind to different cells in various ways and tell our genes to express themselves or not. In addition, there are histones, around which DNA wraps itself. These histones control the degree to which our genes will be expressed depending on how tightly or loosely the DNA wraps around them. These methyl groups and histones are the two main modifiers in epigenetics. Our genome stays the same throughout our entire lives, but our epigenetic markers change based on life experiences, consequently deciding which genes get expressed or not. We not only pass our DNA onto our children, but also our epigenetic tags, which change based on day-to-day experiences. Diet, stress, and prenatal nutrition can affect the genes that are passed onto future generations through these epigenetic markers.

Literature Review

Introduction

The underlying idea of passing on our experiences through our epigenetic tags can be connected back to nutrition, metabolism, and obesity. Scientists have recently found evidence that our lifestyle choices, like smoking or eating too much, can change our epigenetic tags, causing the genes for obesity to express themselves too strongly (TIMES, 2010). Thus, what and how much we eat today can affect us for years to come. Researching the connection between epigenetics, metabolism, and nutrition is especially important today, in a world where obesity is becoming a prominent issue. According to a Gallop poll (2013), obesity rates have increased in all major demographic and socioeconomic groups except for the 18-29 age group. The cause for the recent spike can be attributed to environmental factors; specifically, overeating and largely sedentary lifestyles. However, research tells us that many people also have a genetic predisposition toward obesity (Kirchner, 2013). This means that not only are our lifestyle choices contributing to the recent spike in obesity, but there is also an underlying genetic problem which we are further amplifying through epigenetic modifications. Although we cannot change our genes, changing our diet could change our epigenetic tags in a positive way, which would benefit us and future generations.

Connection to Metabolism

One way in which metabolism can be connected to epigenetics is through methylation. A recent paper by Chiacchiera et al. (2013) discusses how various metabolic pathways control epigenetic reactions. The same paper states that methylation-based epigenetic reactions are a factor in determining metabolic pathways and concluded that the quality and quantity of our diet and caloric intake can impact our genes epigenetically. Knowing more about which nutrients affect specific methylation-based reactions could tell us how we can improve our diets so we can maximize our metabolic potential. Through lab work, we can study various human epigenomes and see how specific diets and foods affect methylation at the molecular level. This could show us how certain food groups affect specific methyl groups in positive or negative ways. For example, according to the National Institute for Health (2006), leafy green vegetables are rich in folate, a dietary source of methyl which can help increase metabolic processes. Through laboratory research, it is possible to find more nutrients that affect these metabolic epigenetic markers in beneficial ways. With this research, a diet rich in metabolic-boosting nutrients could be developed that would help people with slower than normal metabolic rates stabilize their metabolism. Not only do methylation-based reactions have an effect on epigenetics, but so do histone patterns.

Metabolism can also be connected to epigenetics through histone patterns. Katada et al. (2012) discuss the epigenetic changes in histones and how histones can act as metabolic sensors, manifesting metabolic changes into gene expression. By changing how tightly or loosely the DNA is wound around histone proteins, histones control how much or how little of our genes are expressed. This article delves into the details of how exactly these changes in histones translate to gene expression while trying to determine how much of an impact our nutrition can have on our histone patterns. This research helps support the theory that what we eat today can impact us and future generations metabolically through epigenetic modifications. Researchers need to determine which major nutrients have an effect on histone modifications by studying their reactions. Depending on the type of modification that occurs, research would be able to determine each nutrient’s beneficial or detrimental effects on histones. Based on the complexity of the reaction, pharmaceutical companies could also develop synthetic drugs that could mimic the process by which nutrients bring about this beneficial effect in histones. However, this depends on the complexity of the process by which nutrients modify histones.

Prenatal Nutrition

Researchers have also found that maternal dietary fat, folic acid, and protein alter epigenetic regulation of specific genes in offspring. Specifically, the methylation of particular fetal tissues has been connected to the risk of developing diabetes and breast cancer (Burdge, 2012). Researchers have yet to study these methylation-based epigenetic reactions at a molecular level, but it is crucial for further applications. Research needs to be conducted at a molecular level in order to discern which molecules and processes are involved. A recent study worked with mice that had a unique gene called the agouti gene, which gives mice a propensity for obesity and diabetes (Dollinoy, 2008). One group of pregnant mice consumed a diet rich in B vitamins, and the other group received no prenatal nutrition. The first group produced mice that were of normal weight and not prone to diabetes, whereas the second group produced mice that were prone to both obesity and diabetes. In this study, the B vitamins acted as methyl donors, causing methyl groups to attach to the agouti gene more frequently, thereby altering its expression. Based on this research, researchers should also look into prenatal nutrition for humans. Depending on which nutrients are found to have a beneficial impact epigenetically, researchers should consider revamping prenatal nutrition to maximize the benefits. If we find that there are other nutrients that help with metabolic rates but are not already given to pregnant women, we should reconsider which prenatal vitamins are currently being provided and whether or not it would be beneficial to give pregnant women a wider variety of nutrients.

Connection to Diseases

The relation between epigenetics, metabolism and nutrition is also connected to various diseases. Research shows that nutrition and stress can create an impression on genes that leaves a lasting mark (Portha et al., 2013). This lasting impression can manifest into metabolic and cardiovascular diseases, among others. The most important message this research can give us is that we are impacting our own bodies and future generations with our current nutrition-based decisions. The effects of malnutrition begin from birth. Further research shows that low birth weight increases the risk for developing diseases like diabetes and cardiovascular diseases (Basel, 2007). This research suggests that poor nutrition, even before birth, can lead to epigenetic changes which can manifest into diseases later in life, but it does not tell us how to avoid developing these diseases through good nutrition. Further research needs to be done in order to determine how these changes occur on a molecular level so that we can determine which lifestyle changes will have the greatest impact.

The research that has been done so far on the connection between epigenetics, metabolism, and nutrition encompasses a variety of information but it is also very scattered. From reviewing these sources, an overall connection has been established between epigenetics, metabolism, and nutrition; however, further research needs to be performed in order to find an exact relation at the molecular level. Through this additional research, we can determine how to use this information to help combat the issue of obesity in America.

Guidelines to Combat Obesity

Ultimately, the primary step in combating obesity is educating the public. First and foremost, before discussing the genetic aspects, the importance of daily exercise and a good diet should be emphasized. As stated earlier, the major causes of obesity in America are poor diet and a largely sedentary lifestyle. Lack of motivation and hectic lifestyles stop people from exercising or eating properly. They do not have time to get their daily exercise or make a healthy meal. The number of fast food restaurants in America contributes to this problem. There are also people who are successful in accomplishing the difficult goal of losing weight but they are unable to maintain their weight. There are many factors that attribute to the skyrocketing levels of obesity in America, including genetics, lifestyle, inactivity, unhealthy diets, medical problems, and socioeconomic factors. Most people have issues stemming from more than one of these subjects, which is why trying to solve the problem of obesity is so difficult. There are factors that have yet to even be discovered that are related to obesity. For example, many Americans are vitamin-D deficient but do not realize it. Recent studies have shown that low vitamin D levels can trigger the winter response, which includes accumulation of fat and lower metabolic rates (Foss, 2009). Another aspect many people do not think about is how their lifestyle affects others. The public should be educated on the epigenetic effects of their actions. Many people might be unaware that their actions now can affect their children or future children through the DNA they pass on. The public should also be informed on all the diseases that could affect them or future generations due to their obesity. Everyone can learn about this important information through organizations like the Department of Health. We can spread the word through the media: magazines, newspapers, TV, radio advertisements, public service announcements, etc. The reality of epigenetics might make people see their diets in a new light, because they would realize that they are not only putting themselves in danger, but future generations as well.

The second step would be to create a feasible dietary regimen that works to an individual’s advantage. As stated earlier, after determining which nutrients modify these epigenetic modifiers, it would be possible to isolate the nutrients that have a metabolic-related impact. Those nutrients with a beneficial metabolic-related effect would be the recommended nutrients and foods for a better diet. A program could be developed that would take the metabolic rate of a person, compare it to the normal rate for gender and age group, and come up with a dietary plan. For example, foods and nutrients that are known to naturally increase metabolism include: egg whites, iron, chili peppers, caffeinated coffee, green tea, milk, whole grains, and lentils (“9 Foods,” 2015). This is just a handful of the known foods that increase metabolic rates. Individuals have different needs based on their metabolic processes and should have individualized dietary plans. Based on their metabolic rates and nutrient deficiencies, the program would tell them which nutrients they need to increase to normalize their metabolic rate and the best way to get their recommended value. Although this sounds like another useless weight loss program, it would be different because the results can be backed up by precise laboratory research.

The last step would be to tackle the issue at an epigenetic level. The process by which nutrients help increase metabolic rates can be studied, isolated, and then manipulated through the use of pharmaceutical drugs. If the exact reaction that occurs on a molecular level when nutrients increase metabolism through epigenetic modifications is determined, synthetic drugs could be developed that would tweak certain metabolic enzymes related to histones and methyl groups. This would help us alter any genetic predispositions people have toward developing various types of diseases or speed up a slow metabolism. Looking at the impact on histones and methyl groups, research should be done on a molecular level to see how these nutrients brought about this beneficial change.

Using research found on how these nutrients increase metabolism, pharmaceutical companies could create a synthetic drug that would mimic these properties and bring about these same beneficial effects in an amplified manner. On a molecular level, there has to be a specific process by which these nutrients manipulate histones and methyl groups, and whether the process involves an enzyme or some other molecule still needs to be determined. The amplification method would depend on what type of process is uncovered, but if it is enzyme induced, a substrate could be added to make the reaction go faster. Ideally, we hope to find the nutrients that boost metabolism and mimic the process with the creation of a new synthetic drug to help normalize metabolism for those with slower than normal rates.

Conclusion

The biggest problem that needs to be tackled is researching the exact hormones, enzymes, or molecules that connect epigenetics, metabolism, and nutrition. With this research, drugs that could help people maximize their metabolism can be created, which would benefit many people who feel that they cannot lose weight no matter how much they control their diet and exercise. This research could potentially revolutionize the way people see nutrition. This could help reinforce the idea that a good diet and exercise is beneficial because people will see that a bad diet with no exercise not only affects them but it also affects their children and future generations through epigenetic principles.

Diseases caused by obesity, like type 2 diabetes, coronary heart disease, hypertension, arthritis, and cancer depend on where fat is deposited, but they are also affected by genetics (Kirchner, 2013). Based on this information, many people struggling with obesity might think that changing their lifestyle would do nothing. They might extrapolate that if obesity is written in their genes, they cannot change. Many people feel hopeless because they have tried everything, from a good diet to exercise, but nothing has worked. However, many times, slow metabolic reactions are the reason for weight gain and this research aims to solve that problem at the roots. Not only will epigenetics determine which nutrients will help boost metabolism in the long run, but it will also determine the process behind increasing metabolic rates. This information will help to make synthetic drugs that maximize metabolic rates in people who have less than satisfactory rates. People feel helpless in their bodies because of their genes, but with this research, the problem can be solved. If these steps are taken to educate the public and to start this special type of weight loss program based on epigenetic research, we can combat obesity. Overall, this would decrease the amount of obesity that currently exists in the United States, which in turn would also help decrease the likelihood of developing obesity-related diseases. Everyone can benefit from this research because epigenetic modifications happen at all stages in life. With epigenetics, it is never too late to make a change.