COMMENT pubs.acs.org/est
Obesogens, the Exposome, and ES&T
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an chemicals to which we are exposed, even in the womb, make us fat? That is the hypothesis of Bruce Blumberg, University of California at Irvine, who first coined the term “obesogen”. Blumberg and colleagues published several recent papers in endocrinology journals documenting the effects of tributyltin on fetal development, which predispose stem cells to become fat cells. Other researchers report the alteration of adipose tissue development, food intake, and lipid metabolism —dramatic effects potentially caused by organotins, perfluorooctanoic acid (PFOA), diisobutyl phthalate, bisphenol A (BPA), and other xenobiotic chemicals found in the environment. Effects of endocrine disrupting chemicals (EDCs) have long been known including the classic case of the hormone diethylstilbestrol, given to women during problem pregnancies. Now obesogens are a new and troubling class of EDCs, only recently entering our vernacular and potentially affecting many more people. Endocrine glands include the ovaries, pancreas, adrenal glands, thyroid, parathyroid, and the thymus. They release hormones—chemical messengers—to regulate metabolism as well as sexual reproduction. EDCs interfere with this natural hormone signaling. Thus, obesogens are a special class of EDCs targeting lipid metabolism. Most disturbing to me is the potential for “transgenerational effects”. We know that exposure to pregnant mammals can affect the mother, the fetus, and even the germ cells of the fetus, leading to effects on the third generation (grandchild). Now researchers are considering whether transgenerational inheritance to the fourth generation (great-grandchildren) is possible from a single prenatal exposure. Theo Colborn et al.’s seminal book, Our Stolen Future (Penguin Books: New York, 1996), shook the entire world of environmental health. Yet, we know a great deal more today. In Our Stolen Future, the authors emphasized EDC effects on reproduction, the immune system, and our nervous system and brain, but next-to-nothing was purported regarding lipid metabolism. Obesogen-type effects were not even mentioned. Now we have an epidemic of obesity, diabetes, and metabolic syndrome. In the U.S. alone, obesity has increased from a 12% of the population in 1990 to 25% today. If chemicals cause even a fraction of this problem, it is a dramatically important discovery. Still, we should not expect that exogenous, environmental pollutants are responsible for a large fraction of obesity and other metabolic disorders (e.g., diabetes, heart disease, and hypertension). Rather, based on recent exposure science, one finds innumerable contributing causes and complexities, including the wide variability among susceptible populations. The “exposome” is a measure of all exposures that an individual accrues in a lifetime. It is exceedingly difficult to measure due to extreme variability in space and time of a single individual’s exposure. Yet, it is a novel and useful concept, helping us to explore the progression of disease from an absorbed dose to a targeted health outcome, including the use of genetic information on susceptibility factors and biomarkers along the way. If we knew the exposome, we could use data-mining techniques and r 2011 American Chemical Society
high-performance computing to unravel the intricacies of how exposures interact with genomics (and other “-omics” technologies) to produce full-blown disease. It is complicated. For example, the diversity of microbes in our gut, part of the so-called “microbiome”, plays a key role in digestion. Ten times more cells exist “on us” and “in us” from associated microbiota than our own human cells! Recently, Qin and co-workers (Nature 2010, 464, 59 67, doi 10.1038/nature08821) discovered over 3.3 million microbial genes in the gut of 124 individuals from Europe. Humans share most of the same microorganisms, profoundly affecting our nutrition and metabolism, but it is the differences among individuals and variability within a single life-span that likely affects the progression of disease. Logic might dictate that the diversity of so many microorganisms living intimately inside us and aiding in our nutrition would be far more important than exposure to low concentrations of environmental pollutants in our food, air, and water. But the jury is still out on that question. In 2004, ES&T created a new category in our Table of Contents, “Ecotoxicology and Human Environmental Health”. It grew from an increasing coverage of eco-effects over the years and from an emphasis on fate and transport of contaminants. To that end, we embrace this new science of the exposome, which includes exposure to certain environmental pollutants traditionally a focus of this journal. Some of these same chemicals may prove to be endocrine-disrupting obesogens, and we will cover the exposure and risk science of the transport to humans, and the treatment technologies to prevent it. Jerald L. Schnoor
’ AUTHOR INFORMATION Corresponding Author
[email protected].
Published: March 11, 2011 2517
dx.doi.org/10.1021/es200688s | Environ. Sci. Technol. 2011, 45, 2517–2517
