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Although often thought of as resulting from a somewhat “simple” discrepancy between energy consumption and energy expenditure, experts now agree that obesity often results from complex interactions among biology (e.g., genetics and epigenetic modification), behavioral patterns, and environmental factors—especially when they occur during critical or sensitive periods of development such as during fetal growth, infancy, and early childhood. There is also growing evidence that during these periods of high plasticity, our bodies can be “programmed” to respond to environmental and behavioral factors such as dietary intake patterns in ways that influence long-term disease risk. This concept, often referred to as the “developmental origins of health and disease,” has gained significant traction in the past few decades and is thought to help explain a relatively hefty portion of individual variation in chronic health and disease risk. For instance, slow growth in utero may be advantageous to infants born into food-poor environments, but when these infants experience rapid growth during the first few months of life they have higher rates of childhood obesity and chronic disease when they become adults. To explore the evolving science examining how genetics/epigenetics, environment, and developmental stage interact to affect risk of childhood obesity, the Institute of Medicine’s Food and Nutrition Board and the National Research Council’s Board on Children, Youth, and Families, together, hosted a workshop in Washington, DC, in early 2015. The objectives of this workshop were 3-fold:
Highlights of this 2-d workshop, which was chaired by Dr. Shari Barkin (Monroe Carell, Jr., Children‘s Hospital at Vanderbilt University, Nashville, TN), have been published by the National Academies Press and are summarized here.
A centerpiece of the workshop and its objectives was a thoughtful and user-friendly figure illustrating the overlapping and multifaceted relations among multiple environmental and biological levels, stresses such as environmental toxicants and maternal exposures, human and microbial genetics and epigenetics, and period of the lifespan. This illustration, referred to as the “early origins of obesity” model is shown here as Figure 1. Also, a common thread woven throughout the workshop was the topic of how epigenetic modification, first described by the African American biologist, Dr. Ernest Just, in the early 1900s, and generally defined as persistent changes in gene expression not related to variation in DNA sequence, might represent a critical mediator in determining both acute and long-term risk of obesity. However, whether experimental findings, especially in humans, indicate causal compared with correlational or confounding associations is not always clear. Indeed, reverse causality is highly possible in this scenario. Consequently, use of experimental animal models is often critically instructive in this regard, and prospective studies are needed to “help infer causality, assessing epigenetic variation within the context of genetic variation, and focusing on tissue-specific epigenetic patterning.”
Substantial dialogue was also devoted to the combined importance of both maternal and paternal nutrition and other exposures before conception, as well as maternal and infant nutrition and health during both gestation and the postpartum period. Economic and health disparities are likely drivers in this regard and, therefore, must be factored into public health programs and policies.
Opportunities for intervention and prevention were recognized as including use of DNA methylation differences (and other epigenetic modifications) at birth as predictive biomarkers of later adiposity and addition of bioactives such as leptin to infant formula. The potential importance of gastrointestinal microbiota, factors that influence their community structure, and metabolic capabilities thereof were also key components of the overarching discussion. Additional prospective, adequately powered studies will be needed to understand more completely how early microbial presence and function affect childhood and adult energy balance.
Workshop participants concluded with a facilitated discussion concerning gaps in data and research needs, especially as they relate to how epigenetics is related to childhood obesity. The importance of plasticity and “gene control” in terms of mammalian fitness was emphasized as well as gaining more in-depth knowledge of tissue-specific genetic modification during early life. In addition, more information is needed concerning mothers’, fathers’, grandmothers’, and grandfathers’ life histories (including nutritional status) and exposures to endocrine disrupters, hormones, and other factors that might be involved in programming health. Also emphasized were the challenging realities that 1) what we say we eat is not always what we actually eat, 2) nutrient requirements vary among individuals, 3) birth weight can be influenced by many factors other than alterations in maternal nutrition, and 4) early programming is much more complicated than epigenetics. The importance and lack of information on sleep were also noted. In conclusion, Barkin stated, “the potential power of epigenetic science is understanding what we can do today to affect the health of future generations as well as what we can do today to mitigate or modify the effects on this generation.”
A free on-line version of this report can be found at http://www.iom.edu/Reports/2015/Epigenetics-WIB.aspx. Details about the workshop, including the agenda, videos of the presentations, and additional reading material, can be found at http://www.iom.edu/Activities/Nutrition/FetalDevelopment/2015-FEB-26.aspx. A comprehensive summary of the workshop will be publicly available in a forthcoming publication published by the National Academies Press.