Developmental origins and environmental influences—Introduction


  • Jerrold J. Heindel,

    Corresponding author
    1. Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
    • Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709
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  • Edward Levin

    1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina
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  • This article is a US government work and, as such, is in the public domain in the United States of America.

Obesity is a growing concern worldwide. The prevalence of obesity has risen dramatically in developed countries over the past 2–3 decades and has reached epidemic proportions in the United States. It is mainly considered to be caused by overeating and lack of physical activity on a background of genetic predisposition. However, there is much uncertainty related to the etiology of obesity. The Department of Health and Human Services (DHHS) and the National Institutes of Health (NIH) have released documents detailing the extent of obesity and what can/should be done to reduce it in the United States and thereby improve the health of the American people (DHHS; NIH). What is clear is that obesity is notoriously difficult to treat; thus, prevention is critical. In this regard, a new paradigm for prevention has emerged in recent years that evolved from the idea that environmental factors in early life and in utero can have profound influences on lifelong health (e.g., the fetal basis of adult disease). The initial paradigm dealt with the effect of profound nutritional deficiencies in utero and its relationship to later risk of chronic diseases, including obesity. Thus, until recently, the major environmental influence on birth weight and subsequent obesity has been considered to be nutrition.

There is increasing evidence that in utero exposure to environmental chemicals at environmentally relevant concentrations, either alone or in concert with nutritional influences, may alter developmental programming resulting in functional deficits that do not become apparent until later in life, at which time they appear as increased susceptibility to disease and dysfunction. A recent review (Baillie-Hamilton,2002) presented a provocative hypothesis to explain the obesity epidemic. This article presents data showing that the current epidemic in obesity cannot be explained solely by alterations in food intake and/or decrease in exercise. Although there certainly is a genetic component of obesity, genetics cannot have changed over the past few decades, which suggests that environmental changes might be responsible for at least part of the current obesity epidemic. Thus obesity, like other diseases and dysfunctions, is due to gene-environment interactions, and part of the environment may be exposures in utero or neonatally to environmental chemicals. Chemicals most likely to have an effect on the incidence of obesity are those that have endocrine-disrupting activity, especially those that can mimic estrogens, as estrogens are important in fat cell development and activity. In addition, there are chemicals that have been shown to have growth-promoting properties: properties that have been exploited by the farming industry. There are also chemicals that control fat cell metabolism and appetite on the sympathetic nervous system.

To assess the state of science for a possible role for in utero exposure to environmental chemicals in the etiology of obesity, a symposium was held at Duke University and sponsored by the National Institute of Environmental Health Sciences (NIEHS) and the Duke University Integrated Toxicology Program. Some of the talks given at this symposium are presented in this issue (the entire symposium can be viewed at: The articles presented herein as short reports cover an introduction to the obesity epidemic, the role of in utero nutrition in obesity, some basic biology of fat cells and their control, and several talks related to the effects of in utero exposure to environmental agents on later onset of obesity in animal models. It should be noted that at this point there are minimal data linking in utero exposures to environmental chemicals and subsequent sensitivity to obesity later in life. The goal of this symposium and the articles herein is to show that there are data available that show proof-of-concept in animal models. Many questions remain, including: will these experiments be replicated, will the data in animals extrapolate to hazards in humans, and at what exposure levels? Will toxicology and environmental health sciences play a major role in addressing the obesity epidemic via reduction in exposures to environmental chemicals in utero and throughout life? Will this area of research be a fruitful one for intervention and prevention studies of obesity? Only time and more research will tell, but the present data open the door.