Examining a Developmental Approach to Childhood Obesity The Fetal and Early Childhood Years: Workshop Summary (2015) / Chapter Skim
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2 Conceptual Overview of the Role of Epigenetics in Childhood Obesity
2 Conceptual Overview of the Role of Epigenetics in Childhood Obesity
Pages 9-22
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From page 9... ...
This chapter summarizes the Session 1 presentations and discussion. Robert Waterland of the Baylor College of Medicine described what is arguably the clearest example of the causal role of epigenetic dsyregulation in obesity in an animal model: genetically identical agouti mice developing into either lean (brown)
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. Figure 2-1 Regardless of causality, Baccarelli expressed hope that in the future epigenetic markers at birth can be used to raster newborns at increased risk bitmapped identify of childhood obesity.
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Even as many cells are replaced over time by progenitor cells, their progenitor cells "remember" to generate the same epigenetic markers. Another way to think about epigenetics is to remember that the word "epigenetics" literally means "above genetics." Epigenetic mechanisms are gene regulatory mechanisms layered on top of the DNA sequence information.
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From page 12... ...
and others, it remains unclear whether histone modifications have the definitive epigenetic characteristics of mitotic heritability, that is, whether specific established histone modifications can convey information over mitosis. On the other hand, autoregulatory transcription factors have been recognized for decades as being able to function epigenetically (Riggs and Porter, 1996)
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From page 13... ...
, with the obese mouse having a very low level of DNA methylation at the Avy locus and her lean sister being very highly methylated at the same locus. Alleles that behave like the Avy, that is, with dramatic inter-individual variation in DNA methylation even among genetically identical indi iduals, v are called metastable epialleles.
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From page 14... ...
He identified several obstacles to understanding how epigenetic dysregulation contributes to human obesity, not the least of which is that genetic variation is an important determinant of epigenetic variation. If one was to conduct a case control study of obese versus lean individuals, one could certainly find epigenetic differences between the two groups, he said.
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From page 15... ...
First, controlled studies in appropriate animal models are urgently needed to advance researchers' understanding of epigenetic mechanisms underlying the developmental programming of obesity. For example, Waterland pointed to the significant advantages of using inbred mouse models: the removal of genetic variation as a factor, the ability to observe a single life span from embryonic development to adulthood in only 1 year, and the ability to obtain all relevant tissues.
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From page 16... ...
The marks can be written in either pencil or pen, with notes written in pen representing, in the genome, permanent epigenetic markings established during fetal life. Notes written in pencil, in contrast, like the methylation markings on inflammatory genes, are reprogrammable and can change within a matter of minutes.
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From page 17... ...
, Baccarelli proposed that fetal life exposure programs the epigenome at birth, but that the epigenome at birth is modifiable and can change in postnatal life. Fetal exposures can potentially be correlated to risk of obesity, and its sequelae, via the epigenome, include high maternal body mass index (BMI)
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From page 18... ...
. Over time, studies became larger, confidence intervals shrank, and the odds ratios being reported suggested that the increased risk associated with the polymorphism was actually only 40 percent higher.
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What are the benefits to patients and to society? PANEL DISCUSSION WITH SPEAKERS In the panel discussion following Baccarelli's presentation, workshop participants considered a range of topics: the tissue specificity of epigenetic markers and changes, nutritional exposure to dietary methyl donors, the impact of assisted reproductive technologies on epigenetic patterning, and the temporary nature of many epigenetic markers.
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I find it just amazing that there seems to be more regulation about what goes into our breakfast cereal than what is the specific composition of the media that are used for these early embryos during the in vitro fertilization process." Early studies suggested that individuals conceived via assisted reproductive technologies run a higher risk of certain developmental diseases. However, according to Waterland, it is still unclear whether those diseases result from the process itself or from epigenetic aberrations that existed in either the sperm or the egg and that contributed to the infertility in the first place.
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From page 21... ...
Moderator Matthew Gillman closed the session by suggesting that Relton's question be kept in mind for the remainder of the workshop. As he rephrased it, "Even if DNA methylation or other epigenetic processes are transient, could they set in motion a programmatic phenomenon?
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