The Role of Environmental Exposures in Obesity
Are Environmental Chemicals Making It Harder to Control Our Weight?
BY KELLY LENOX, NIEHS
Although exercising and healthy eating play crucial roles in the fight against obesity, current research is reshaping our understanding of the complex roots of the global obesity epidemic. At the National Institute of Environmental Health Sciences (NIEHS) and elsewhere, scientists are examining the interactions between genetic factors and environmental exposures that may be contributing to the obesity problem.
STEVE MCCAW, NIEHS
“This problem is not restricted to the U.S. or technologically advanced countries, but is increasing in less-developed countries as well,” said NIEHS Director Linda Birnbaum at the IOM workshop held recently at NIEHS.
“We want to try to tease apart that interaction [and] reinforce the concept that obesity—with its attendant comorbidities, such as diabetes and metabolic syndrome—is a multifactorial outcome,” said NIEHS Director Linda Birnbaum to an international audience that gathered in March at the NIEHS campus (Research Triangle Park, North Carolina) for an Institute of Medicine (IOM) two-day workshop on “The Interplay Between Environmental Exposures and Obesity.” Birnbaum, who is also the director of the National Toxicology Program (NTP), posed the question that presenters would shed light on: “We have to ask whether environmental chemicals are making it harder for us all to control our weight.”
“Only when we understand the complex origins of the likelihood of becoming obese will we be able to deal with this huge health and economic problem,” said Frank Loy, chair of the group that convened the workshop—the IOM Roundtable on Environmental Health Sciences, Research, and Medicine. Nearly 600 people registered for the Webcast, and more than 100 attended in person to hear researchers from academia, government, public health, and industry discuss the issue.
Scientists shared results of their investigations ranging from multigenerational studies of the effects of specific chemicals, to large-scale epidemiologic research, to economic analyses (see sidebar).
Kristina Rother (National Institute of Diabetes and Digestive and Kidney Diseases) discussed in vitro and in vivo studies showing that noncaloric sweeteners appear to increase insulin secretion and adipogenesis and decrease the sense of reward. “There is no convincing evidence that artificial sweeteners prevent or alleviate obesity,” she said. (J Clin Endocrinol Metab 97:2597–2605, 2012)
Molecular toxicologist Scott Auerbach (NTP) shared data-mining approaches for identifying chemicals to test for possible obesity and diabetes outcomes. The National Center for Advancing Translational Science (NCATS) PubChem database (http://www.ncats.nih.gov/research/tools/preclinical/pubchem/pubchem.html) provides public access to data collected through the ToxCast (http://www.epa.gov/ncct/toxcast/) and Tox21 (http://www.epa.gov/ncct/Tox21/) projects, which are collaborative efforts between NIEHS and the NCATS Chemical Genomics Center. The researchers selected biological processes associated with obesity and then obtained expert recommendations on which ToxCast assays were most relevant to those processes. Another approach, called sentinel chemical correlation, is a data-driven method used to identify groups of chemicals with similar biological action. These and other approaches can be useful in screening chemicals for further study.
Obesity Society President Nikhil Dhurandhar (Texas Tech University in Lubbock, Texas) shared research that linked adenovirus 36 infection with a greater potential for preadipose tissue to differentiate into adipose tissue. He showed an intriguing series of maps in which the pattern of obesity increase in the United States resembled the spread of an infectious agent (influenza) more than it did the spread of a noninfectious disease (asthma).
Other presenters included Barbara Corkey (Boston University School of Medicine, Boston), whose research suggests that food additives and environmental factors might be triggering metabolic changes such as pancreatic beta cells secreting too much insulin; Beverly Rubin (Tufts University, Medford, Massachusetts), who has found evidence linking perinatal bisphenol A (BPA) exposure in mice to increases in inflammation and systemic insulin resistance; and John Rogers, a microbiologist with the U.S. Environmental Protection Agency, who said that low concentrations of BPA and other agents could stimulate obesity, but increasing doses can lead to other toxic mechanisms that can ultimately drive weight down.
During discussions, participants raised a wide range of issues such as neurological factors that affect appetite and activity, changes in the composition of meat and produce over the past 50 years, and decreases in the duration of sleep. Many speakers echoed a familiar refrain: The traditional focus on energy balance explains only part of the obesity epidemic.
The IOM event Web site for the event (http://www.iom.edu/chemicalsandobesity) includes presenters’ slides and video recordings of the presentations. The Roundtable summary report, to be completed later in 2015, will also be available on that site.
1. Framing the problem: Public- and environmental-health overviews highlighted the multiple pathways involved in the risk of obesity.
2. Life-span view: Focusing on chemical exposures from pregnancy through adulthood, speakers addressed effects of prenatal and early-life exposures to endocrine-disrupting chemicals as well as links among exposures, the onset of puberty, and obesity.
3. Biologic pathways: Scientists presented approaches to uncovering how environmental chemicals may disturb biologic pathways, including high- throughput screening, studies of adipose-tissue function and inflammation, and discussed effects of environmental chemicals on energy metabolism and insulin secretion.
4. Nutrients, food additives, and antibiotics: Researchers shared their latest findings on the role of infectious agents, antibiotics, and food ingredients in the development of obesity.
5. Research needs and policy solutions: Presenters and the audience engaged in open discussion of new research directions and policies that might reduce exposure to chemicals associated with obesity.