Adipogenic Effects of a Combination of the Endocrine-Disrupting Compounds Bisphenol A, Diethylhexylphthalate, and Tributyltin

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Abstract

Objective: The food contaminants bisphenol A (BPA), diethylhexylphthalate (DEHP), and tributyltin (TBT) are potent endocrine-disrupting compounds (EDC) known to interfere with adipogenesis. EDC usually act in mixtures and not as single compounds. The aim of this study was to investigate the effects of a simultaneous exposure of BPA, DEHP, and TBT on mesenchymal stem cell differentiation into adipocytes. Methods: Multipotent murine mesenchymal stem cells (C3H10T1/2) were exposed to EDC mixtures in high concentrations, i.e. MIX-high (10 µmol/l BPA, 100 µmol/l DEHP, 100 nmol/l TBT), and in environmentally relevant concentrations, i.e. MIX-low (10 nmol/l BPA, 100 nmol/l DEHP, 1 nmol/l TBT). The exposure was performed either for the entire culture time (0-12 days) or at distinct stages of adipogenic differentiation. At day 12 of cell culture, the amount of adipocytes, triglyceride content (TG), and adipogenic marker gene expression were analyzed. Results: MIX-high increased the development of adipocytes and the expression of adipogenic marker genes independently of the exposure window. The total TG amount was not increased. The low-concentrated EDC mixture had no obvious impact on adipogenesis. Conclusion: In EDC mixtures, the adipogenic effect of TBT and DEHP predominates single effects of BPA. Mixture effects of EDC are not deducible from single compound experiments.

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Worldwide trends in childhood overweight and obesity.

Youfa Wang, Tim Lobstein (2005)

Obesity has become a global epidemic but our understanding of the problem in children is limited due to lack of comparable representative data from different countries, and varying criteria for defining obesity. This paper summarises the available information on recent trends in child overweight and obesity prevalence. PubMed was searched for data relating to trends over time, in papers published between January 1980 and October 2005. Additional studies identified by citations in retrieved papers and by consultation with experts were included. Data for trends over time were found for school-age populations in 25 countries and for pre-school populations in 42 countries. Using these reports, and data collected for the World Health Organization's Burden of Disease Program, we estimated the global prevalence of overweight and obesity among school-age children for 2006 and likely prevalence levels for 2010. The prevalence of childhood overweight has increased in almost all countries for which data are available. Exceptions are found among school-age children in Russia and to some extent Poland during the 1990s. Exceptions are also found among infant and pre-school children in some lower-income countries. Obesity and overweight has increased more dramatically in economically developed countries and in urbanized populations. There is a growing global childhood obesity epidemic, with a large variation in secular trends across countries. Effective programs and policies are needed at global, regional and national levels to limit the problem among children.

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The epidemiology of obesity.

Cynthia Ogden, Susan Yanovski, Margaret Carroll … (2007)

In the United States, obesity among adults and overweight among children and adolescents have increased markedly since 1980. Among adults, obesity is defined as a body mass index of 30 or greater. Among children and adolescents, overweight is defined as a body mass index for age at or above the 95th percentile of a specified reference population. In 2003-2004, 32.9% of adults 20-74 years old were obese and more than 17% of teenagers (age, 12-19 y) were overweight. Obesity varies by age and sex, and by race-ethnic group among adult women. A higher body weight is associated with an increased incidence of a number of conditions, including diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease, and with an increased risk of disability. Obesity is associated with a modestly increased risk of all-cause mortality. However, the net effect of overweight and obesity on morbidity and mortality is difficult to quantify. It is likely that a gene-environment interaction, in which genetically susceptible individuals respond to an environment with increased availability of palatable energy-dense foods and reduced opportunities for energy expenditure, contributes to the current high prevalence of obesity. Evidence suggests that even without reaching an ideal weight, a moderate amount of weight loss can be beneficial in terms of reducing levels of some risk factors, such as blood pressure. Many studies of dietary and behavioral treatments, however, have shown that maintenance of weight loss is difficult. The social and economic costs of obesity and of attempts to prevent or to treat obesity are high.

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Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population

Antonia M Calafat, Zsuzsanna Kuklenyik, John A. Reidy … (2004)

Bisphenol A (BPA) is used to manufacture polycarbonate plastic and epoxy resins, which are used in baby bottles, as protective coatings on food containers, and for composites and sealants in dentistry. 4-Nonylphenol (NP) is used to make nonylphenol ethoxylates, nonionic surfactants applied as emulsifying, wetting, dispersing, or stabilizing agents in industrial, agricultural, and domestic consumer products. The potential for human exposure to BPA and NP is high because of their widespread use. We measured BPA and NP in archived urine samples from a reference population of 394 adults in the United States using isotope-dilution gas chromatography/mass spectrometry. The concentration ranges of BPA and NP were similar to those observed in other human populations. BPA was detected in 95% of the samples examined at concentrations ≥0.1 μg/L urine; the geometric mean and median concentrations were 1.33 μg/L (1.36 μg/g creatinine) and 1.28 μg/L (1.32 μg/g creatinine), respectively; the 95th percentile concentration was 5.18 μg/L (7.95 μg/g creatinine). NP was detected in 51% of the samples examined ≥0.1 μg/L. The median and 95th percentile concentrations were < 0.1 μg/L and 1.57 μg/L (1.39 μg/g creatinine), respectively. The frequent detection of BPA suggests widespread exposure to this compound in residents of the United States. The lower frequency of detection of NP than of BPA could be explained by a lower exposure of humans to NP, by different pharmacokinetic factors (i.e., absorption, distribution, metabolism, elimination), by the fact that 4-n-nonylphenol—the measured NP isomer—represents a small percentage of the NP used in commercial mixtures, or a combination of all of the above. Additional research is needed to determine the best urinary biomarker(s) to assess exposure to NP. Despite the sample population’s nonrepresentativeness of the U.S. population (although sample weights were used to improve the extent to which the results represent the U.S. population) and relatively small size, this study provides the first reference range of human internal dose levels of BPA and NP in a demographically diverse human population.

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Author and article information

Journal

Journal ID (publisher-id): OFA

Journal ID (pmc): OFA

Journal ID (nlm-ta): Obes Facts

Journal ID (doi): 10.1159/issn.1662-4025

Title: Obesity Facts

Publisher: S. Karger AG

ISSN (Print): 1662-4025

ISSN (Electronic): 1662-4033

Publication date Subscription-year: 2014

Publication date (Print): February 2014

Publication date (Electronic): 31 January 2014

Volume: 7

Issue: 1

Pages: 48-56

Affiliations

Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University, Halle (Saale), Germany

Article

Publisher ID: 358913 Other ID: Obes Facts 2014;7:48-56

DOI: 10.1159/000358913

PMC ID: 5644809

PubMed ID: 24503497

SO-VID: 96dc7750-512a-46d7-8142-6b528320fb3d

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Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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Date received : 04 June 2013

Date accepted : 04 September 2013

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Pages: 9

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Adipogenic Effects of a Combination of the Endocrine-Disrupting Compounds Bisphenol A, Diethylhexylphthalate, and Tributyltin

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Karger: Nutrition and Dietetics

Most cited references 35

Worldwide trends in childhood overweight and obesity.

The epidemiology of obesity.

Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population

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