The prevalence of obesity and its related disorders is currently attaining pandemic proportions, both in the Western and the developing world. Although lifestyle choices are commonly accepted as the main reasons, it has recently been suggested that environmental pollutants may provide an alternative cause. Several man-made chemicals have been shown to facilitate the differentiation into adipocyte at environmentally relevant levels. This process is mediated through different nuclear receptors. The endocrine function of the adipocyte itself is also affected by chemicals. This article provides a compact overview of the implicated chemicals and their modes of action. We also present the current level of evidence, linking exposure to these endocrine disrupting chemicals and obesity and its related diseases.
Flegal, K.M., et al. (2012) Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA, 307, 491-497. doi:10.1001/jama.2012.39
Ogden, C.L., et al. (2012) Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA, 307, 483-90.
Seidll, J.C. (2000) Obesity, insulin resistance and diabetes—A worldwide epidemic. British Journal of Nutrition, 83, S5-S8.
Han, J.C., et al. (2010) Childhood obesity. Lancet, 375, 1737-1748.
Van Gaal, L.F., et al. (2006) Mechanisms linking obesity with cardiovascular disease. Nature, 444, 875-880
Cameron, A.J. et al. (2012) A systematic review of the impact of including both waist and hip circumference in risk models for cardiovascular diseases, diabetes and mortality. Obesity Reviews, 41, 484-494.
Ye-huda-Shnaidman, E., et al. (2012) Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis. Obesity Reviews, 13, 1083-1095.
Lee, E.B. (2011) Obesity, leptin, and Alzheimer’s disease. Annals of the New York Academy of Sciences, 1243, 15- 29.
Rayman, G. and Kil-vert, A. (2012) The crisis in diabetes care in England. BMJ, 15, e5446.
Prentice, A.M. (2001) Overeating: The health risks. Obe- sity Research, 9, 234S-238S. doi:10.1038/oby.2001.124
Baillie-Hamilton, P.F. (2002) Chemical toxins: A hypo- thesis to explain the global obesity epidemic. The Journal of Alternative and Complementary Medicine, 8, 185-192.
Smith, B.S. (1981) Reproductive anomalies in stenoglos- san snails related to pollution from marinas. Journal of Applied Toxicology, 1, 15-21.
Smith, B.S. (1981) Male characteristics on female mud snails caused by antifouling bottom paints. Journal of Ap- plied Toxicology, 1, 22-25.
Matthiessen, P., et al. (1995) Changes in periwinkle (Littorina littorea) populations following the ban on TBT-ba- sed antifoulings on small boats in the United Kingdom. Ecotoxicology and Environmental Safety, 30, 180-194.
Vos, J.G., et al. (2000) Health effects of endocrine-disru- pting chemicals on wildlife, with special reference to the European situation. Critical Reviews in Toxicology, 30, 71-133. doi:10.1080/10408440091159176
Sung, E., et al. (2012) Detection of endocrine disruptors from simple assays to whole genome scanning. International Journal of Andrology, 35, 407-414.
Ballschmite, K., et al. (2002) Man-made chemicals found in remote areas of the world: the experimental definition for POPs. Environmental Science and Pollution Research, 9, 274-88. doi:10.1007/BF02987503
Breivik, K., et al. (2006) Empirical and modeling evi- dence of the long-range atmospheric transport of decabro- modiphenyl ether. Environmental Science & Technology, 40, 4612-4618.
Toft, G., et al. (2008) Menstrual cycle characteristics in European and Inuit women exposed to persistent orga- nochlorine pollutants. Human Reproduction, 23, 193-200.
Pedersen, S.B., et al. (2004) Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution. The Journal of Clinical Endocrinology & Metabolism, 89, 1869-1878.
Krishnan, A.V., et al. (1993) Bisphenol-A: An estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology, 132, 2279-2286.
Masuno, H., et al. (2001) Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. The Journal of Lipid Re-search, 43, 676-684.
Rubin, B.S., et al. (2001) Perinatal exposure to low doses of bisphenol A affects body weight, pat-terns of estrous cyclicity, and plasma LH levels. Environmental Health Perspectives, 109, 675-680.
Somm, E., et al. (2009) Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environmental Health Perspectives, 117, 1549-1555.
Penza, M., et al. (2011) The environmental chemical tri- butyltin chloride (TBT) shows both estrogenic and adi- pogenic activities in mice which might depend on the ex-posure dose. Toxicology and Applied Pharmacology, 255, 65-75.
Rosen, E.D., et al. (1999) PPAR gamma is re-quired for the differentiation of adipose tissue in vivo and in vitro. Molecular Cell, 4, 611-617.
Tontonoz, P. and Spiegelman, B.M. (2008) Fat and be- yond: The diverse biology of PPARgamma. Annual Re- view of Biochemistry, 77, 289-312. doi:10.1146/annurev.biochem.77.061307.091829
Ferré, P. (2004) The biology of peroxisome proliferator- activated receptors: Relationship with lipid metabolism and insulin sensitivity. Diabetes, 53, S43-S50.
Maloney, E.K. and Waxman, D.J. (1999) Trans-activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals. Toxicology and Applied Pharmacology, 161, 209-218.
Lehmann, J.M. (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-acti- vated receptor gamma (PPAR gamma). The Journal of Biological Chemistry, 270, 12953-12956.
Liu, S.C. (2012) Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: A network meta-analysis. Diabetes, Obesity and Metabolism, 14, 810- 820.
Tchoukalova, Y.D., et al. (2012) In vivo adipogenesis in rats measured by cell kinetics in adipocytes and plastic-adherent stroma-vascular cells in response to high-fat diet and thiazolidinedione. Diabetes, 61, 137-144.
Kanayama, T., et al. (2005) Organotin compounds pro- mote adipocyte differentiation as agonists of the perox- isome prolifera-tor-activated receptor gamma/retinoid X receptor pathway. Molecular Pharmacology, 67, 766-774.
Inadera, H. and Shimomura, A. (2005) Environmental chemical tributyltin augments adipocyte differentiation. Toxicology Letters, 159, 226-234.
Zuo, Z., et al. (2011) Tributyltin causes obesity and he- patic steatosis in male mice. Environmental Toxicology, 26, 79-85.
Kirchner, S., et al. (2010) Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Molecular Endocrinology, 24, 526-539.
Bility, M.T., et al. (2004) Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters. Society of Toxicology, 82, 170-182. doi:10.1093/toxsci/kfh253
Feige, J.N., et al. (2007) The endocrine disruptor mono- ethyl-hexyl-phthalate is a selective peroxisome prolifera- tor-activated receptor gamma modulator that promotes adipogenesis. The Journal of Biological Chemistry, 282, 19152-19166. doi:10.1074/jbc.M702724200
Casals-Casas, C., et al. (2008) Interference of pollutants with PPARs: Endocrine dis-ruption meets metabolism. In- ternational Journal of Obesity, 32, S53-S61. doi:10.1038/ijo.2008.207
Stahlhut, R.W., et al. (2007) Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult US males. Environmental Health Perspectives, 115, 876-882.
Hatch, E.E., et al. (2008) Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: A cross-sectional study of NHANES data, 1999-2002. Environmental Health, 3, 27.
Wauters, M., et al. (2001) Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women. International Journal of Obesity and Related Metabolic Disorders, 25, 714-720.
Turer, A.T. and Scherer, P.E. (2012) Adiponectin: Mecha- nistic insights and clinical impli-cations. Diabetologia, 55, 2319-2326.
Boberg, J., et al. (2008) Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats. Toxicology, 250, 75-81.
Wei, J., et al. (2011) Peri-natal exposure to bisphenol A at reference dose predisposes offspring to metabolic syn- drome in adult rats on a high-fat diet. Endocrinology, 152, 3049-3061.
Hugo, E.R., et al. (2008) Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environmental Health Perspectives, 116, 1642-1647.
Heindel, J.J. and vom Saal, F.S. (2009) Role of nutrition and environmental endocrine disrupting chemicals during the perinatal period on the aetiology of obesity. Molecular and Cellular Endocrinology, 304, 90-96.
Newbold, R.R., et al. (2007) Developmental exposure to endocrine dis-ruptors and the obesity epidemic. Reproduc- tive Toxicology, 23, 290-296. doi:10.1016/j.reprotox.2006.12.010
Beyerlein, A., et al (2011) Is low birth weight in the causal pathway of the associa-tion between maternal smo- king in pregnancy and higher BMI in the offspring? European Journal of Epidemiology, 26, 413-420.
Tang-Péronard, J.L., et al. (2011) Endo-crine-disrupting chemicals and obesity development in humans: A review. Obesity Reviews, 12, 622-636.
Karmaus, W., et al. (2009) Maternal levels of dichlorodiphenyl-dichloroethylene (DDE) may increase weight and body mass index in adult female offspring. Occupational and Environmental Medicine, 66, 143-149.
Gladen, B.C., et al. (2004) Prenatal DDT exposure in re- lation to anthropometric and pubertal measures in adoles- cent males. Environmental Health Perspectives, 112, 1761- 1767.
Elobeid, M.A., et al. (2010) Endocrine disruptors and obesity: An examination of selected persistent organic pol- lutants in the NHANES 1999-2002 data. International Journal of Environmental Research and Public Health, 7, 2988-3005.
Dirinck, E., et al. (2011) Obesity and persistent organic pollutants: Possible obesogenic effect of organochlorine pesticides and polychlorinated biphenyls. Obesity, 19, 709-714.
Hectors, T.L., et al. (2011) Environmental pollutants and type 2 diabetes: A review of mechanisms that can disrupt beta cell function. Diabetologia, 54, 1273-1290.
Henriksen, G.L., et al. (1997) Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemio- logy, 8, 252-258.
Everett, C.J., et al. (2007) Association of a polychlori- nated dibenzo-p-dioxin, a polychlorinated biphenyl, and DDT with diabetes in the 1999-2002 National Health and Nutrition Examination Survey. Environmental Research, 103, 413-418.
Lee, D.-H., et al. (2006) A strong dose-response relation between serum concentrations of persistent organic pollu- tants and diabetes: Results from the National Health and Examination Survey 1999-2002. Diabetes Care, 29, 1638- 1644. doi:10.2337/dc06-0543
Lee, D.-H., et al. (2007) Extended analysis of the association between serum concentrations of persistent orga- nic pollutants and diabetes. Diabetes Care, 30, 1596- 1598. doi:10.2337/dc07-0072
Lee, D.-H., et al. (2010) Low dose of some persistent organic pollutants predicts type 2 diabetes: A nested case- control study. Environmental Health Perspectives, 118, 1235-1242. doi:10.1289/ehp.0901480
Lee, D.H., et al. (2007) Relationship between serum con- centrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutri-tion Examina- tion Survey 1999-2002. Diabetologia, 50, 1841-1851.
Gladen, B.C., et al. (2000) Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. Journal of Pediatrics, 136, 490-496. doi:10.1016/S0022-3476(00)90012-X
Welshons, W.V., et al. (2006) Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinol- ogy, 147, S56-S69. doi:10.1210/en.2005-1159
Wolstenholme, J.T., et al. (2012) Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression. Endocrinology, 153, 3828-3838.