Obesity & Heredity, Part 4: Epigenetics

I first heard about epigenetics from Dr. Theodore Belfor, the man behind the adult palate expansion device called the Homeoblock.  It is his opinion that epigenetics will be the most important field of science in the next decade.  In brief, epigenetics is the study of  the changes that take place within the epigenome – literally, "on top" of the genome – due to environmental factors, such as food and pollution, without affecting the DNA sequence.  Here's a more lengthy explanation from a website  published by a European group who call themselves “The Epigenome Network of Excellence:”

Conrad Waddington (1905-1975) is often credited with coining the term epigenetics in 1942 as “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being”. Epigenetics appears in the literature as far back as the mid 19th century, although the conceptual origins date back to Aristotle (384-322 BC). He believed in epigenesis: the development of individual organic form from the unformed. This controversial view was the main argument against our having developed from miniscule fully-formed bodies. Even today the extent to which we are preprogrammed versus environmentally shaped awaits universal consensus. The field of epigenetics has emerged to bridge the gap between nature and nurture. In the 21st century you will most commonly find epigenetics defined as 'the study of heritable changes in genome function that occur without a change in DNA sequence.'

Take home quote from above: “...epigenetics has emerged to bridge the gap between nature and nurture.”  This is extremely important in the study of health and nutrition, as there are many questions of what brings about good health and poor health in the context of inheritance, none of which can be fully answered without evaluating specific individual choices – dietary, environmental, etc. – made within each generation (which affects future generations).   In other words, nurture – how we are taken care of as children and how we take care of ourselves as adults  – is what molds and shapes nature – the way our bodies and minds express themselves epigenetically, which is then potentially passed to our children.

How do epigenetic changes take place?  The Epigenome Network of Excellence reporter, Brona McVittie, puts it this way:

The genetic blueprint, like a complex musical score, remains lifeless without an orchestra of cells (players) and epigenotypes (instruments) to express it... Epigenetic factors include both spatial patterns, such as the arrangement of DNA around histone proteins (chromatin), and biochemical tagging...With some 30 000 genes in the human genome, the importance of silence, as with any orchestral performance, must not be underestimated...As cells develop, their fate is governed by the selective use and silencing of genes... Failure to silence genes can produce a hazardous cacophony.

What does all of this have to do with obesity?  Well, scientists have discovered that epigenetic changes in mice that are pregnant mothers can directly impact the health of the offspring.  How?  By turning on or off specific genes through dietary or environmental means.  One of these health effects, in addition to cancer and diabetes, is a tendency of the offspring to become obese as adults.  In one study, if a single gene, called the “agouti gene,” is overexpressed through the failure to suppress another gene (Avy), it greatly influences the ultimate health of the offspring (emphasis mine):

Failure to epigenetically suppress the Avy gene during development causes the agouti gene to be ectopically overexpressed later in life. This high level of agouti expression in essentially all tissues causes numerous downstream metabolic and endocrine effects that ultimately affect gross biological end points such as obesity and survival. This agouti overexpression and its physiological effects have been termed the yellow agouti obese mouse syndrome. This syndrome includes a yellow or mottled yellow coat color, altered metabolism and obesity from a young age. It also results in adult diabetes, increased cancer susceptibility and, by 24 mo of age, twice the mortality seen in normal mice.

Interestingly, whether or not a mouse becomes obese seems to depend on the levels of methyl-donating substances, such as folic acid (a vitamin naturally found in high amounts in organ meats, many kinds of legumes, and dark leafy greens).  The reason behind this has to do with the way that DNA passes information to cells in the body -- a process called  DNA methylation.  Whether or not certain genes are expressed has a lot to do with this process.  Without enough methyl-donating substances, such as the B-vitamins, betaine, choline, SAM-e and genistein (from soybeans), DNA methylation is disturbed and abnormal cell expression, along with switching on or off certain genes, results.  You can see why folic acid supplementation is recommended for pregnant women and why women in traditional cultures consume "sacred" foods rich in methyl-donating nutrients, such as liver, before and during pregnancy.

So, if obese people supplement their diet with folate or genistein, can they reverse the epigenetic changes that may have brought about their obesity?  Short answer: we don't know.  In animal studies, there's more certainty.  Here's what Randy Jirtle, an expert in epigenetics, has to say:

Weaver et al. (Nat. Neurosci. 7: 847-854, 2004) at McGill University, however, have shown recently that maternal nurturing behavior can stably alter the epigenotype in rat pups soon after birth. Moreover, these epigenetic changes are reversible in adulthood following methionine supplementation or treatment with histone deacetylase (HDAC) inhibitors (Weaver et al.Proc. Natl. Acad. Sci. USA 103: 3480-3485, 2006). Thus, data supporting the reversal of environmentally induced epigenetic changes via dietary supplementation or pharmaceutical therapy in adulthood is mounting.

The implications for humans are far-reaching.  Perhaps someday we'll have a way of epigenetically treating obesity, diabetes, and cancer.  For now, the best we can do is eat a nutrient-dense real-foods diet while avoiding processed and refined foods -- the foods that have most likely brought about our health dilemmas in the first place.

For a great overview of epigenetics, check out PBS Nova's educational page on the subject.  Also, here's a nice website by the University of Utah.
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SIDEBAR: Is Plastic Making Us Fat?

Aside from diet, another significant factor in the tendency of the agouti mice to become obese comes from the mother's exposure to biosphenol-A (BPA), a common plastic found in many food and beverage containers.  Here's Randy Jirtle again to explain:

We have demonstrated recently that when female pregnant mice are exposed to BPA, the incidence of yellow Avy offspring is markedly increased because DNA methylation of the agouti gene is decreased (Dolino et al.,Proc. Natl. Acad. Sci. USA 104: 13056-13061, 2007). BPA also epigenetically alters gene expression of at least one other gene, indicating a genome-wide effect. Yellow agouti mice become obese in adulthood and have a high probability of developing diabetes and cancer. Consequently, BPA exposure leads to adult diseases in agouti mice by altering the epigenome during the earliest stages of development—a condition that can be counteracted by maternal nutrient supplementation with methyl-donating substances (folic acid, etc.) or genistein.

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SIDEBAR: Weston A. Price & Epigenetics

Epigenetics may seem obvious to folks out there who are familiar with Darwin's theory of evolution.  “Of course our bodies and minds are shaped by our environment; and of course we evolve (or devolve) throughout time and generations.  That's the way nature works!”  The big difference, as far as I can tell, is that unlike DNA, epigenetic changes actually take place within one lifetime, not over eons of evolution.  The way the epigenome appears to be altered is by dramatic changes in environment, particularly diet.  Think Nutrition and Physical Degeneration or Pottenger's Cats.

Actually, one might say that Price and Pottenger recognized epigenetics when they observed physical degeneration in the people and animals they respectively studied, although they didn't call it that.  The changes in facial structure and lowered immunity in their studies appeared to be a direct result of poor diet generation after generation.  Once again, during one lifetime, the epigenome can be altered significantly.  Could it be that the mothers and fathers eating a modern diet and the cats eating cooked food altered their epigenome and then passed on these traits on to the next generation?  Is this why each generation appeared to be progressively worse than the last?  The field of epigenetics suggests this is the case.
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Obesity & Heredity, Part 3: Why Are Thin People Not Fat?

Below is an intriguing BBC documentary, called "Why Are Thin People Not Fat?"  In this film, ten thin people who have no history of obesity overeat whatever foods they want for several weeks and the results are evaluated at the end of the experiment.  One especially interesting facet of the documentary is the fact that the Asian participant gains the least weight of all the participants and also appears to have the most elevated metabolism.  Could it be that his genes are more pure -- i.e. less degeneration in his family -- than the others?  Watch and decide for yourself!

Obesity & Heredity, Part 2: You Are What Your Parents Ate

Stephan Guyenet at Whole Health Source wrote a brilliant blog series a few months back, called “The Body Fat Setpoint,” in which he describes the mechanisms behind an individual's ability to maintain a  very specific weight.  No matter how much a person overeats and how much weight is gained, his or her body is simply primed to be at this “setpoint” and will “defend” it diligently through natural fat regulation mechanisms.  Stephan references a study where:

They overfed lean and modestly overweight volunteers 50% more calories than they naturally consume … After 6 weeks of massive overfeeding, both lean and overweight subjects gained an average of 10 lb (4.6 kg) of fat mass and 6.6 lb (3 kg) of lean mass...  Following overfeeding, subjects were allowed to eat however much they wanted for 6 weeks. Both lean and overweight volunteers promptly lost 6.2 of the 10 lb they had gained in fat mass (61% of fat gained), and 1.5 of the 6.6 lb they had gained in lean mass (23%).  

To me, the most interesting aspect regarding human overfeeding studies like this is that, once the overfeeding period has ended, the participants return to their original weight without dieting.  As Stephan indicates, this means that our bodies have the inherent ability to maintain our “normal weight.”  Refer to the post I wrote on tribal fattening practices and the fact that the fattened women who refuse to overeat their real foods diet return to a healthy weight in short order.  Normal weight, however, appears to be different for every individual. For example, when a person has a normal weight – a setpoint – that, by all standards, can be seen as obese, we are left with the question of just why in the heck this is happening.  Why does the body insist on remaining in such a biologically abnormal state?

Many scientists and researchers claim that leptin – a hormone which regulates appetite – plays a key role in obesity, as many people who are overweight exhibit low levels of the hormone.  Much research has been conducted on the validity of this theory and it is now recognized that leptin resistance – in which the body can no longer can recognize when it has had enough food – is what enables a person to eat more than they need, thus leading to obesity and keeping that person obese.  And, surprise, surprise: artificial fructose is a prime culprit in leptin resistance because fructose doesn't stimulate leptin (or insulin for that matter).  No stimulation, no appetite regulation.

Skinny Jeans & Skinny Genes

Okay, so leptin appears to play a role in weight maintenance.  That's all fine and good, but why can some people eat and drink whatever they want -- including artificial fructose -- without affecting their body composition while some people become obese?  This is where I believe heredity comes into play.  Depending on what stage of degeneration a person is in – first, second, or third generation of processed food consumption, let's say, and/or what a person's mother ate while pregnant with him/her – obesity can be more or less of a potential complication.

In my case, for example, my mother wasn't overweight when I was in the woom and neither of my parents are overweight now.  This is despite consuming a lot of high-fructose corn syrup and omega-6 vegetable oils for much of their lives.  I was raised on this typical industrial diet and never experienced issues of overweight as a child, and I have no issues now.  At age 18, I altered my diet and cut out processed foods, which is how I eat now, eight years later.  But my older brother, now age 29, has continued to eat our childhood foods without gaining significant weight.  Other health problems aside, my family has no weight issues.  Is there something about us genetically that is behind all of this?  I think it's a strong possibility.  And maybe this is because, like Don Gorske, we may have a closer-to-pure hereditity.  We are not yet degenerated to the point where the disease of obesity has set in.

In contrast, I know of a few childhood friends (two brothers) who now appear to be on the receiving end of metabolic discord through familial degeneration.  In their twenties now, they are both experiencing weight problems.  They also drink a lot of beer and don't seem to have the best diet in the world.  Observing their parents, the mother has been overweight for at least half of her life (including several years before becoming pregnant) and the father has always been slim, despite drinking a lot of beer and not having the best diet in the world just like his sons.  Why is dad slim while having very similar dietary habits to his overweight sons?  Are his genetics more pure and less degenerated – less overall processed food consumption – than the mother's genes, which appear to have a hereditary predisposition to being overweight?  This may be the case, and it would explain the weight issues of the two sons, as they would inherit half of their mother's genes.        

Several studies have been done evaluating the role heredity may play in obesity.  The most compelling subset of these studies are those that include data from adopted children, their adoptive parents, and their biological parents.  Here's an abstract from one of these of these studies, called “Genetic contributions to human fatness: an adoption study:”

A strong relationship was found between the degree of fatness of biologic mothers and that of their adult offspring who had been separated from their mothers at birth and adopted during the first year of life. This relationship persisted even after age, height, and possible confounding environmental factors were controlled. There was little evidence for either selective placement on the basis of parental fatness or gene-environment interaction. There was no relationship between the degree of fatness of adoptive parents and that of the adoptees.

It's interesting that the weight of the child was directly affected by the weight of the biological mother and is not affected by the environment of the adoptive home.  This supports my theory on the two sons who I described above.  There is, however, one glaring confounding factor in all of this talk about obesity and heredity, and that is the increasing consumption of high-fructose corn syrup in the last 30 years.  This amazingly effective human fattener was not significant in the industrialized diet until 1980, when Coca-Cola officially began adding this biochemically engineered sweetener to its popular soft drink.  This also happens to be the time when obesity levels really began to take off.  Check out the graph below from the paper, “High-fructose corn syrup in beverages may play a role in the epidemic of obesity:”

So does that mean that heredity may not be as important as diet in the development of obesity?  Not necessarily.  I believe the two go hand-in-hand and, as I said earlier, it's possible that it is heredity and the diet of the mother which determines susceptibility to the effects of HFCS or other processed foods.

So what lesson have we learned here?  Well, there's still a lot of questions, but I think we can safely say that some people have more difficulty with weight than others, and that reason may not necessarily be connected to dietary choices in all cases.  Rather, there are several lifetimes of degeneration that may be influencing each individuals propensity to gain – and keep on – the fat.

For solutions to inherited susceptibility to obesity, I refer you back to Stephan, who I think provides some good advice.  As far as my recommendations, the best change anyone can make in their diet to make a difference in health, and perhaps body composition, is to simply eliminate the four nasties: artificial fructose, gluten, trans fats, and vegetable oils.  Eat real food.  And please, please, please raise your children on real foods so they don't have the same health difficulties that many of us adults have!  

Obesity & Heredity, Part 1: Don Gorske

For better or for worse, we inherit much of the body composition tendencies of our parents.  This can be argued as merely adopting their food habits, which directly affects our health, and I believe that's a big part of why our bodies are the way they are.  However, there are most certainly genetic predispositions to certain body shapes and sizes, as well.  Often times, I focus on diet as the #1 instigator of health and disease, but when it comes to issues of overweight and obesity I often find myself wondering just how much genetics can play a role in whether a person is thin or fat, muscular or lanky, apple or pear-shaped.  Many of us know folks who can eat whatever the heck they want without any apparent health effects or significant body composition changes.  

Case in point, Don Gorske, the infamous McDonald's enthusiast who has eaten 24,000 Big Macs since 1972.  Despite this indulgence -- and the sodas that come with it -- Gorske appears to be in good health.  (I say “appears” because he is not overweight and has good cholesterol numbers; not so sure about his teeth, triglycerides, HDL:LDL ratio, VLDL levels or other markers of health.)  He has a full head of dark hair, walks every day, and also has a positive outlook on life.  Arguably, these are signs of good health.  How can this be?  Isn't fast food one of the prime suspects in modern disease?  Could this mean that fast food is off the hook?  Well, before you go out gorging on McDonald's because of one man's seeming success on such fare, read on.

Mr. 180, Matt Stone, recently blogged about Gorske, pinpointing dietary, philosophical, and hereditary  reasons as to why this man's physical health seems to be unaffected by the foods he eats.  Of all the reasons listed by Matt, I believe heredity to be the most important factor.  For one thing, as Matt says in his post, Gorske grew up “...in cow country and didn't start eating fast food until age 18 ...”  Developmentally speaking, this Big Mac-lover had a head start in good health -- especially if we consider that he only started eating fast food after his body and metabolic tendencies were well-established.  And while it's interesting to observe Gorske's apparent well-being and question the assumption that fast food is detrimental to our health, the picture would not be complete without full consideration of his unique heredity.  Perhaps he is the fortunate heir of health not-far-removed from that of our ancestors.  What of his genetics, his childhood health, his parents' and their parents' health?

Unfortunately, I don't have access to this information, but I would hazard a guess that his parents were closer to a traditional diet than not for most of their lives, and that they were maybe the first or second generation of degeneration.  In contrast, many of us have parents or grandparents who were well on their way to degeneration during their life time and this directly affected our health -- epigenetics influenced strongly by diet. (See section below, “Degeneration in the Cafeteria.”)  Maybe some of us, like Gorske, are able to avoid some of the dramatic metabolic changes seen today -- namely obesity -- simply because our parents and grandparents hadn't quite reached that particular stage of degeneration.  Obesity, if we think about the very low historic levels and the high levels of today, appears to be a stage of degeneration that comes after maybe three generations of poor food habits.  It also appears to be in direct connection with the consumption of the modern franken-foods -- artificial fructose, trans fats, white flour, vegetable oils.    

Whatever the case may be, it's evident that obesity is an abnormal human state brought about by heredity, which is influenced by dietary changes.  What's interesting, however, is that some people -- like Don Gorske-- due to perhaps a closer-to pure heredity, are able to escape the effects of poor food habits during their lifetime.  How their children might fare is another question.    

You know what would be an awesome experiment?  Taking a bunch of thin people who appear to do just fine on junk-food, like Gorske, and feeding them lots and lots of food and seeing how quickly they gain weight, how their metabolism reacts, and whether or not they return to their normal weight when the experiment is over.  Maybe this would provide answers as to why thin people are thin.  That post is up next.

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SIDEBAR: Degeneration in the Cafeteria

Imagine a line at a cafeteria with a limited amount of food.  There's (1) the traditional foods of our ancestors: raw dairy, grass-fed meats, fish, fresh grains, fruits and vegetables; there's (2) a mixed-diet of these traditional foods with some processed foods (mainly sugar and white flour); then there's (3) the factory-raised meats, white flour, artificial fructose, and rancid vegetable oil-laden diet of today.  First in line, our great grandparents, enjoyed a diet primarily of traditional foods and experienced good health.  Second in line, their children (our grandparents) approached the front of the line and much of the traditional foods had already been eaten by their parents, so they began eating some white flour and sugar with some ill health effects, notably lowered immunity and dental disease.  Third in line, these childrens' children (our parents) arrived at  the food and they were left with more white flour and sugar than traditional foods; they developed physical deformities from nutritional deficiencies and might have developed some issues with weight and diabetes as well as other degenerative diseases, depending on their parents' food choices.  That brings us to the last ones in line (the 20 and 30-somethings of today) who are left with the most processed of all processed foods: high-fructose corn syrup, rancid vegetable oil, trans fats, and the like.  These poor folks not only have a poor diet, but may inherit the traits of their parents 100-fold, possibly becoming obese and diabetic at an early age, in addition to a slew of health problems that come along with being at the end of a long line of degeneration.  Below is a (purely theoretical) visual representation of this. 

Tribal Fattening Practices

While in America "thin is in," in some cultures around the world "fat is where it's at." One such culture can be found in the desert-streaked country of Mauritania, located in West Africa. Here, the true marker of beauty and health in a woman is the amount of rolls she has. But there's one problem: human beings eating normal amounts of natural foods don't get obese and overweight, and the common foods available in West Africa include raw goat's milk, meat, millet, couscous, dates, peanuts, and other whole foods. While most of us in the Western world can easily become fat through years of eating fattening, unnatural, metabolism-altering foods like high-fructose corn syrup, trans-fats, and high-gluten white flour, the Mauritanian people don't have such "luxuries" -- so they resort to good old-fashioned force-feeding to accomplish the task.

The Mauritanian fattening practice, called leblouh, takes place when young women enter a tiny sandstone hut. Inside resides an old woman, the "fattener," whose primary job in the community is to make sure these young women (sometimes beginning as young as 5-years-old) become plump and, thus, attractive and suitable for marraige.

Obvious moral and ethical implications of this practice aside, I thought it would be interesting to find out just how much food is utilized to accomplish the fattening. I was surprised to find out that these women typically are force-fed -- to the point of nasuea and vomiting at times -- a whole-foods diet of up to 16,000 calories. This includes four meals per day of:

...crushed dates and peanuts with couscous and oil ... cloying, egg-size balls of around 300 calories apiece. Each girl eats about 40 per day, along with 12 pints of goat's milk and gruel ... (Source)

To bolster the fattening process, the women also must not get any exercise whatsoever, remaining in the huts for several years until they are married off. Additionally, because the task of eating such inordinate amounts of food is so physically challenging to the young women, the old woman "fattener" threatens to beat them if they refuse to eat.

Because the Mauritanian women are limited to traditional foods, which lead to satiety rather quickly due to high nutrient content and are difficult to overeat, some have sought out methods to increase their appetite unnaturally to be able to gain those extra pounds of beauty. One such method is the purchase of certain pharmaceuticals:

Sold secretly at city markets, they include hormones used to fatten camels and chickens, and steroids for asthma and cancer ... (Source)

The difficulty inherent in these traditional peoples' ability to gain weight while eating whole foods challenges the notion, once again, that carbohydrates lead to obesity. Here we have a culture whose only way of fattening young women is by force-feeding them massive amounts of proteins, carbohydrates, and fats. If to fatten the young women it was only necessary to emphasize carbohydrates in the diet, as Gary Taubes and other low-carb proponents might suggest, then why must the women be forced to eat excessive amounts food to become overweight? Why not just eat millet and couscous and dates? Many modernized folks seem to have no trouble at all gaining unneeded weight while eating far less than 16,000 calories. Yet these Mauritanian women must resort to appetite increasing drugs or the threat of a beating while eating about that much food to do the same:

Although hardly skeletal at 5'6" and 180 pounds, Hawer [a 26-year-old Mauritanian woman] says she has trouble piling on weight, and was teased by plumper girls as a teenager. Recently, her husband told her that he "didn't like sleeping with a bag of bones. Desperate to be bigger, Hawer uses drugs to aid weight gain." (Source)

It's the quality of food that's the difference. Traditional versus modern food. High-fructose corn syrup, one the great fatteners in the indutrialized nations, would be a prized commodity in Mauritania.

One other interesting observation is that the older women in the culture, who have already gone through the fattening process during their younger years and have resumed eating a normal amount of traditional foods, appear to be at a healthy weight. Did they diet to lose their weight? I doubt it. Below is a picture of women who are campaigning against the practice of leblouh. All have gone through the leblouh in their youth, and none of them remain overweight: