The Rise of Obesogens: Chemical Exposures and the Obesity Epidemic
The rate of obesity is on the rise, both globally and in the U.S.1 In the U.S., statistically significant increases were observed in all age groups from the period 1976-1980 to 1988-1994. The percentage of children declared clinically obese has risen dramatically, from 7% of children ages 6-11 in 1980 to nearly 20% in 2008. Obesity among children 12-19 years old increased from 5% to 18% during the same period.2,3 Obesity is closely linked to type 2 diabetes, which is also on the rise,4 as well as with risk factors for the development of cardiovascular disease.5
Various causes of the obesity epidemic have been discussed over the past decades.
Life habits, such as sedentary habits and consumption of high calorie foods, are frequently pointed to as drivers of the increase. The environment’s interaction with an individual’s genetic makeup is another potential driver—and an increasing body of evidence supports this hypothesis. One view is that the interaction between genetics and the modern environment work to intensify an individual’s propensity towards developing obesity, acting via early metabolic programming that occurs in the womb. Another is that the environment plays a different role in obesity—via exposure to chemicals in the environment, whether due to exposure in the womb, or a lifetime of exposure.
A number of specific environmental exposures have been linked with obesity, including maternal smoking during pregnancy and several endocrine-disrupting chemicals.5 In 2002, Baillie-Hamilton reviewed data on the obesity epidemic and suggested that the increase coincided with a marked increase in the usage of industrial chemicals, including pesticides, over the past 40 years.6 The term “obesogen” was coined in 2006 by two researchers, Felix Grün and Bruce Blumberg, to refer to chemicals that disrupt normal development and control over fat cell proliferation and energy balance.5
Pesticides as obesogens
Two recent studies from the laboratory of Bruce Blumberg examined the effects of the pesticides triflumizole and tributyltin using animal models and human cell lines.7,8
- Triflumizole (TFZ) The fungicide TFZ is widely used on both food and ornamental crops, and while it is not particularly toxic or carcinogenic, it appears to promote the pathway leading to fat cell production. Pregnant female mice exposed to low doses of TFZ in their drinking water gave birth to offspring with significantly increased stored fat. Stem cells collected from the fat tissue of the offspring were found to have been “reprogrammed” to favor development into fat cells, rather than being equally likely to develop into fat or bone cells. This reprogramming of the stem cells suggests that prenatal exposure to TFZ predisposes stem cells to become fat cells. Another experiment from this study suggested that the pathway affected by TFZ is the gene that is the “master regulator” of fat cell production, known as peroxisome proliferator activated receptor gamma (PPARg).
- Tributyltin (TBT) TBT is used as a fungicide. Previous research on TBT suggested that prenatal exposure increases fat storage in mice, acting via the master regulator of fat cell production PPARg, discussed above.9 New work on TBT suggests that there is a transgenerational effect from prenatal TBT exposure. Although only the first generation was exposed to TBT, effects were observed in that generation’s offspring and the following generation as well. These effects included increased fat tissue storage, increased fat cell size and number, and the reprogramming of cells to favor generation of fat cells. In addition to these effects, effects on the liver were observed, such as upregulated expression of genes in the liver that are known to be involved in fat storage and transport.7 Upregulated expression of the genes indicates a higher level of activity, suggesting that there was a high level of activity around the functions of fat storage and transport. The liver plays a key role in the breakdown of fats in our bodies.
The observed effects of just two pesticides that have been identified as obesogens indicate a larger problem with our evaluation of chemicals used in agricultural applications. As noted earlier, chemical exposures in our environment begin in the womb. How can we limit our exposure to chemicals—many of which act at low doses and can have long-term impacts on development?10
From a 2012 interview with Bruce Blumberg featured in Environmental Health Perspectives, Blumberg suggested that it is “probably wise and beneficial at any stage of your life to minimize exposure to such chemicals. So in my house we eat organic food as much as possible. We minimize plastic... [and] the amount of processed food that we eat.”11
EPA is now evaluating a number of chemicals for their potential endocrine-disrupting effects through its Endocrine Disruptor Screening Program.12 However, the agency has been slow to act to limit our exposure to endocrine-disrupting chemicals such as obesogens. EPA evaluation of these chemicals is a good thing, but we must call for swifter action. EPA’s risk assessment practices should incorporate consideration of low-dose effects and impacts on development. Leading endocrine disruptor researchers made concrete recommendations to strengthen the Endocrine Disruptor Screening Program in 2012.13 It is time for EPA to act on those recommendations now.
1. Mokdad, A. H. et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289, 76–79 (2003).
2. Ogden, C. L. Prevalence of Obesity and Trends in Body Mass Index Among US Children and Adolescents, 1999-2010. JAMA: The Journal of the American Medical Association 307, 483 (2012).
3. National Center for Health Statistics Health, United States, 2011: With Special Features on Socioeconomic Status and Health. (U.S. Department of Health and Human Services, 2012).
4. U.S. Department of Health and Human Services National Diabetes Information Clearinghouse.
5. Grun, F. Environmental Obesogens: Organotins and Endocrine Disruption via Nuclear Receptor Signaling. Endocrinology 147, s50–s55 (2006).
6. Baillie-Hamilton, P. F. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 8, 185–192 (2002).
7. Chamorro-García, R. et al. Transgenerational Inheritance of Increased Fat Depot Size, Stem Cell Reprogramming, and Hepatic Steatosis Elicited by Prenatal Obesogen Tributyltin in Mice. Environ. Health Perspect. (2013).doi:10.1289/ehp.1205701
8. Li, X., Pham, H. T., Janesick, A. S. & Blumberg, B. Triflumizole is an obesogen in mice that acts through peroxisome proliferator activated receptor gamma (PPARγ). Environ. Health Perspect. 120, 1720–1726 (2012).
9. Grün, F. et al. Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol. Endocrinol. 20, 2141–2155 (2006).
10. Vandenberg, L. N. et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr. Rev. 33, 378–455 (2012).
11. Ahearn, A. What Do We Know about Obesogens? with Bruce Blumberg. Environmental Health Perspectives 120, (2012).
12. U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP)
13. Zoeller, R. T. et al. Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society. Endocrinology 153, 4097–4110 (2012).
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