{"id":1339,"date":"2011-04-20T22:12:07","date_gmt":"2011-04-21T03:12:07","guid":{"rendered":"http:\/\/blogs.edf.org\/nanotechnology\/?p=1339"},"modified":"2024-02-12T11:01:14","modified_gmt":"2024-02-12T16:01:14","slug":"could-these-chemicals-make-my-grandchild-look-fat","status":"publish","type":"post","link":"https:\/\/blogs.edf.org\/health\/2011\/04\/20\/could-these-chemicals-make-my-grandchild-look-fat\/","title":{"rendered":"Could these chemicals make my grandchild look fat?"},"content":{"rendered":"

Richard Denison, Ph.D.<\/em>, is a Senior Scientist.<\/em><\/p>\n

In an earlier post by my colleague Dr. Jennifer McPartland<\/a>, she described new research that is linking certain chemical exposures to the rising epidemic of diabetes and obesity.\u00a0 Some of that research, mainly conducted in laboratory animals, is revealing that when a mother is exposed to such chemicals before or during pregnancy, her offspring<\/em> are more likely to suffer from diabetes and obesity as they mature.<\/p>\n

How might such a proclivity toward development of diabetes and obesity later in life be transferred from one generation to the next, from mother to child?<\/p>\n

In a word, epigenetics<\/a>.\u00a0\u00a0<\/p>\n

The prefix \u201cepi-\u201c comes from the Greek, and means \u201con top of.\u201d\u00a0 So what tops genetics?\u00a0 Isn\u2019t it at the root of all things biological?<\/p>\n

Epigenetics is a huge and rapidly expanding area of biological research and discovery.\u00a0 The journal Science<\/em>, devoted an entire special section to it last October<\/a>. \u00a0I won\u2019t even try to do it justice here.\u00a0 But here\u2019s the basic concept.\u00a0 Each of the cells in each of our bodies has the exact same DNA, the \u00a0identical sequence, in our chromosomes.\u00a0 Yet as we develop from a fertilized egg to countless billions of cells, those cells \u2013 all with the identical DNA \u2013turn into more than 200, radically different types of cells with very distinct functions.<\/p>\n

How epigenetics works<\/strong><\/p>\n

A key mechanism by which this miracle happens, it turns out, is through modifications to the structure of our DNA.\u00a0 These modifications to DNA are not <\/em>changes to its inviolable sequence of nucleotide pairs, known as mutations; rather, the expression of genes and other DNA functions can be altered by \u201cmarking\u201d the DNA.\u00a0 Such \u201cmarks\u201d may be added in any of several different ways.\u00a0 For example, there are specialized enzymes that add methyl groups to DNA \u2013 a process called \u201cmethylation\u201d \u2013 so as to alter the timing or extent of expression of a gene.\u00a0 Similarly, the binding of proteins called histones to the DNA in specific ways is thought to be another epigenetic mechanism.<\/p>\n

Such changes in one cell can then be propagated to other cells through plain old cell division as the organism grows.\u00a0 So, for example, we know certain genes are turned on or off that cause a cell to differentiate into a bone cell or fat cell.\u00a0 When that cell divides, it produces more bone or fat cells.<\/p>\n

But here\u2019s the real kicker:\u00a0 Epigenetic changes, like mutations, are heritable<\/em> \u2013 that is, they can be passed from one generation to the next.<\/p>\n

Think about that:\u00a0 Some factor affects the environment in which a cell\u2019s DNA exists, and that factor can change, not the DNA sequence itself, but the behavior of that DNA, and that change can affect in turn not only the person or other organism in which it first happens but in their offspring too. \u00a0Research indicates epigenetic changes can be relatively stable<\/a>.<\/p>\n

Epigenetic \u201cevolution\u201d has been well-documented in plants, fungi and invertebrates<\/a> , and growing evidence from studies in laboratory animals suggests it can occur in mammals as well.<\/p>\n

What about people?<\/strong><\/p>\n

Epigenetics is clearly at play in people; otherwise we wouldn’t develop — our cells with their identical DNA wouldn’t be able to differentiate.\u00a0 But showing that epigenetic changes can be transferred between generations in people is particularly challenging.\u00a0 That\u2019s because we live a long time, so demonstrating transfer between generations is, shall we say, logistically difficult.\u00a0\u00a0 We also are genetically diverse, much more so than a strain of mice used in a lab, so it\u2019s difficult to rule out that any observed change is due to genetic rather than epigenetic changes.\u00a0 And, of course, we can\u2019t run intentional experiments on people for ethical reasons.<\/p>\n

Some of the first clues that epigenetics are at work in people came from a study in Sweden<\/a> that relied on 200 years of records of grain harvests.\u00a0 The abundance, or lack thereof, of those harvests was found to correlate with the incidence of diabetes and heart disease in the descendants of those who ate well or went hungry.\u00a0 Bizarrely, the grandchildren<\/em> of men who ate well in the years immediately preceding their entry into puberty had significantly shortened<\/em> life spans compared to the grandchildren of men who had less access to food during those formative years.\u00a0 That\u2019s due to a four-fold increase<\/em> in the death rate resulting from diabetes (and some increase in cardiovascular disease) in the grandchildren of the well-fed ancestors.<\/p>\n

Is that wild or what?<\/p>\n

Now, some studies in laboratory animals have documented that the diet of mothers during pregnancy can alter not only the body characteristics of her offspring, but also the methylation pattern of genes in her offspring that are known to be involved in controlling metabolism.\u00a0 That kind of epigenetic effect of maternal diet is far more significant than most genetic changes \u2013 because it operates far faster, within a single generation.<\/p>\n

To date, little analogous evidence has been available in people.\u00a0 Studies as far back as the 1970s<\/a> found that women experiencing famine during pregnancy correlated with obesity in their offspring when they reached adulthood.\u00a0 A study of Dutch women who were pregnant while suffering starvation during World War II<\/a> found that their children were more likely to be smaller, as well as to suffer from diabetes, obesity, cardiovascular disease and other health problems. \u00a0\u00a0And their<\/em> children in turn were also smaller than average.<\/p>\n

These fascinating studies don\u2019t necessarily prove epigenetic changes are to blame for the observed effects.<\/p>\n

However, a study by Godfrey et al<\/em>.<\/a> just published in the journal Diabetes<\/em> starts to do just that. \u00a0The researchers examined the methylation patterns of five metabolic control genes in cells drawn from the umbilical cord tissue of healthy babies.\u00a0 (The umbilical cord is composed almost entirely of cells of fetal, not maternal, origin<\/a>.)\u00a0 They then looked for correlations between those methylation patterns and the nutritional status early in their pregnancies of the women who gave birth to those babies.\u00a0 Finally, they followed those babies until they reached the age of 9 years old.<\/p>\n

Here\u2019s what they found:\u00a0 The lower the mothers\u2019 carbohydrate intake was during early pregnancy, the higher was the extent of methylation of certain of those metabolic control genes in their babies at birth \u2013 and the more likely their children were to be overweight at age 9.<\/p>\n

These data strongly suggest a fetal developmental basis<\/em> for later-life obesity.<\/p>\n

This paper cites a body of evidence indicating that genetic factors explain only a part, likely a small part, of the risk of diabetes, obesity and heart disease, and that environmental factors \u2013 in this case, those in the prenatal environment \u2013 play a greater role.<\/p>\n

The authors\u2019 conclusion is a scientist-speak mouthful:<\/p>\n

\u201cOur study shows that specific components of the epigenetic state at birth predict later childhood adiposity. \u2026 The current study implicates the human prenatal environment with epigenetic changes in nonimprinted genes and is the first to link epigenetic status at birth with clinically relevant later phenotypic variation.\u201d<\/p>\n

Translation:\u00a0 Mom doesn\u2019t eat enough during early months of pregnancy \u2026 key genes involved in metabolic control in her baby become more heavily methylated \u2026 and 9 years later, her child is more likely to be overweight.<\/p>\n

So, what does all this have to do with chemicals not normally present in our bodies?\u00a0 My colleague\u2019s earlier post<\/a> started us down that path.\u00a0 Chemicals to which women are exposed before or during pregnancy can become part of the \u201cenvironment\u201d not only for them but for their fetuses.\u00a0 Certain of these chemicals are known to be \u201cobesogens:\u201d When pregnant mice are exposed to them, they disrupt normal biological activity in their fetuses in such a way that later \u201cpromotes fat accumulation and obesity\u201d in their pups.<\/p>\n

A likely mechanism?\u00a0 You guessed it, epigenetics.\u00a0 We\u2019ll have more to say in these pages on this and related topics, so keep coming back.<\/p>\n","protected":false},"excerpt":{"rendered":"

Richard Denison, Ph.D., is a Senior Scientist. In an earlier post by my colleague Dr. Jennifer McPartland, she described new research that is linking certain chemical exposures to the rising epidemic of diabetes and obesity.\u00a0 Some of that research, mainly conducted in laboratory animals, is revealing that when a mother is exposed to such chemicals …<\/p>\n","protected":false},"author":100,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[56100,5009],"tags":[39181,39208,39174,39176],"coauthors":[],"class_list":["post-1339","post","type-post","status-publish","format-standard","hentry","category-emerging-science","category-health-science","tag-diabetes","tag-methylation","tag-epigenetics","tag-obesity"],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/1339","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/users\/100"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/comments?post=1339"}],"version-history":[{"count":1,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/1339\/revisions"}],"predecessor-version":[{"id":12630,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/1339\/revisions\/12630"}],"wp:attachment":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/media?parent=1339"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/categories?post=1339"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/tags?post=1339"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/coauthors?post=1339"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}