News | Science Selection Issue 2 | February 2016 | Vol. 124
Arsenic Exposure and the Western Diet: A Recipe for Metabolic Disorders?
Julia R. Barrett, MS, ELS, a Madison, WI–based science writer and editor, is a member of the National Association of Science Writers and the Board of Editors in the Life Sciences.
Citation: Barrett JR. 2016. Arsenic exposure and the Western diet: a recipe for metabolic disorders? Environ Health Perspect 124:A39; http://dx.doi.org/10.1289/ehp.124-A39
Published: 1 February 2016
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Related EHP Article
Effects of Arsenite Exposure during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Disease in Male Mice
Chronic arsenic exposure is common in many areas worldwide owing to naturally occurring contamination of well water.1 Arsenic has been shown to contribute to various cancers, skin lesions, and cardiovascular disease.1 Epidemiological studies on arsenic and metabolic outcomes such as nonalcoholic fatty liver disease, obesity, and diabetes have yielded mixed results, however,2,3,4,5 although regional variations in factors such as diet could explain the discrepancies. A new mouse study in this issue of EHP suggests that prenatal and early-life exposures to low-level arsenic, combined with a Western-style diet, may induce developmental changes that heighten the risk of future metabolic disorders and nonalcoholic fatty liver disease.6
A small body of evidence indicates that prenatal and early-life arsenic exposures can influence the development of later disease.1,7,8 For instance, studies of Chilean adults who were exposed to high levels of arsenic prenatally and as very young children had unusually high death rates from lung disease and heart attack.8 “This really gave the evidence that developmental [arsenic] exposure, even just in utero or fetal exposure alone, could lead to consequences in adulthood,” says Todd Camenisch, an associate professor of pharmacology and toxicology at the University of Arizona, who coauthored the current study.
Staining with a dye called Oil Red O shows increased lipid accumulation in the livers of mice exposed prenatally to arsenic (IU and IU+), compared with unexposed mice (CTRL) and those exposed only postnatally (PN). In humans, increased lipid accumulation is a risk factor for cardiometabolic disease.
Ditzel et al. (2016)6
In previous research Camenisch and colleagues studied metabolic disease risk in mice exposed prenatally to low-level arsenic.9 In those experiments, offspring of female mice that drank water containing 100 ppb sodium arsenite during pregnancy developed nonalcoholic fatty liver disease and other signs of heightened risk for metabolic syndrome, a constellation of symptoms associated with diabetes and cardiovascular disease in humans.
The current study built on that work by testing how diet might affect metabolic disease risk in animals exposed to low levels of arsenic. To start, one group of pregnant mice was given water containing 100 ppb sodium arsenite. Half their offspring discontinued arsenic exposure at birth (the in utero, or IU, treatment group), while the other half continued exposure (the IU+ treatment group). A second group of pregnant mice received untreated water; half their offspring drank water containing sodium arsenite after weaning (the postnatal, or PN, treatment group), while the other half served as the untreated control group.
All offspring were weaned to a high-fat, high-sugar Western-style diet and weighed weekly. Lipid and glucose metabolism blood tests were conducted at weaning (3 weeks of age), at 5 weeks, and at 9 weeks. At 13 weeks the livers of all offspring were examined for histologic changes, gene expression, lipid content, and enzymatic activity. Male offspring had significantly higher weight gain, so the researchers focused on them for the current analysis.
The results showed that IU and IU+ exposures exacerbated nonalcoholic fatty liver disease in the mice. Disruptions were seen in energy metabolism, specifically impaired glucose control, insulin resistance, increased obesity, and increased blood levels of triglycerides. Effects were not as severe in the IU group as for the IU+ mice, but they were still more prominent than in the PN and control groups.6 “Overall, we were sort of surprised that we had such disruptions,” says Camenisch.
Studies such as this that are designed to identify critical windows of exposure (e.g., prenatally versus postnatally) can help inform effective policies to prevent exposures; dose is another important consideration. Gavin Arteel, a professor of pharmacology and toxicology at the University of Louisville, says one particular strength of this study was the focus on arsenic concentrations that are relevant to human exposure, although including animals on a low-fat diet for comparison might have brought differences into even sharper focus. Arteel, who was not involved in the study, says, “It’s certainly a proof of concept, though, and that’s another strength.”
1. Naujokas MF, et al. The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect 121(3):295–302 (2013), doi: 10.1289/ehp.1205875.
2. Massey VL, et al. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction. Toxicol Appl Pharmacol 284(3):304–314 (2015), doi: 10.1016/j.taap.2015.02.022.
3. Bräuner EV, et al. Long-term exposure to low-level arsenic in drinking water and diabetes incidence: a prospective study of the diet, cancer and health cohort. Environ Health Perspect 122(10):1059–1065 (2014), doi: 10.1289/ehp.1408198.
4. Maull EA, et al. Evaluation of the association between arsenic and diabetes: a National Toxicology Program workshop review. Environ Health Perspect 120(12):1658–1670 (2012), doi: 10.1289/ehp.1104579.
5. Chen Y, et al. No association between arsenic exposure from drinking water and diabetes mellitus: a cross-sectional study in Bangladesh. Environ Health Perspect 118(9):1299–1305 (2010), doi: 10.1289/ehp.0901559.
6. Ditzel EJ, et al. Effects of arsenite exposure during fetal development on energy metabolism and susceptibility to diet-induced fatty liver disease in male mice. Environ Health Perspect 124(2):201–209 (2016), doi: 10.1289/ehp.1409501.
7. States JC, et al. Prenatal arsenic exposure alters gene expression in the adult liver to a proinflammatory state contributing to accelerated atherosclerosis. PLoS One 7(6):e38713 (2012), doi: 10.1371/journal.pone.0038713.
8. Yuan Y, et al. Acute myocardial infarction mortality in comparison with lung and bladder cancer mortality in arsenic-exposed region II of Chile from 1950 to 2000. Am J Epidemiol 166(12):1381–1391 (2007), doi: 10.1093/aje/kwm238.
9. Sanchez-Soria P, et al. Fetal exposure to arsenic results in hyperglycemia, hypercholesterolemia, and nonalcoholic fatty liver disease in adult mice. J Toxicol Health 1:1 (2014), doi: 10.7243/2056-3779-1-1.
Come visit with EHP’s Science Editor, Jane Schroeder, at the 2016 ISEE Meeting in Rome, Italy, from 1–4 September 2016. This is a great opportunity to meet a member of our team, and to learn more about the journal. A number of our Associate Editors will be in attendance as well. Jane is also co-hosting a half-day writing and publishing workshop on 4 September, following the conference.
EHP is pleased to present the abstracts from the 28th annual meeting of the International Society for Environmental Epidemiology (ISEE), held in Rome, Italy, 1–4 September 2016, and hosted by the Department of Epidemiology Lazio Regional Health Service, ASL Roma 1, and the Italian Epidemiological Association. The focus of this year’s conference is current and future challenges in exposure assessment, study design, and data analyses.
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