Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-24T12:52:53.120Z Has data issue: false hasContentIssue false
  • English
  • Français

Obesogens, stem cells and the maternal programming of obesity

Published online by Cambridge University Press:  04 November 2010

B. Blumberg
B. Blumberg*
Affiliation:
Department of Developmental and Cell Biology and Pharmaceutical Sciences, University of California, Irvine, Biological Sciences 3, Irvine, CA, USA
*
*Address for correspondence: B. Blumberg, Department of Developmental and Cell Biology and Pharmaceutical Sciences, University of California, Irvine, 2011 Biological Sciences 3, Irvine, CA 92697-2300, USA. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Obesity and metabolic syndrome diseases have exploded into a global epidemic. Consumption of calorie-dense food and diminished physical activity are the generally accepted causes for obesity. But, could environmental factors expose preexisting genetic differences or exacerbate the root causes of diet and exercise? The environmental obesogen model proposes that chemical exposure during critical developmental stages influences subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that stimulate adipogenesis and fat storage or alter the control of metabolism, appetite and satiety to promote weight gain. Tributyltin (TBT) is a high-affinity agonistic ligand for the retinoid X receptor (RXR) and peroxisome proliferator activated receptor gamma (PPARγ). RXR-PPARγ signaling is a key component in adipogenesis and the function of adipocytes; activation of this heterodimer increases adipose mass in rodents and humans. Thus, inappropriate activation of RXR-PPARγ can directly alter adipose tissue homeostasis. TBT exposure promoted adipocyte differentiation, modulated adipogenic genes and increased adiposity in mice after in utero exposure. These results suggest that organotin exposure is a previously unappreciated risk factor for the development of obesity and related disorders. Based on the observed effects of TBT on adipogenesis, we hypothesized that organotin exposure during prenatal adipose tissue development would create an environment that led to more adipocytes. We observed that the multipotent stromal cell compartment was altered by prenatal TBT exposure leading to an increased number of preadipocytes. This increase in the number of preadipocytes could correspondingly increase the steady state number of adipocytes in the adult, which could favor the development of obesity over time.

Keywords

adipocyteendocrine disruptermultipotent stromal cellobesityobesogenorganotinPPARγ
Type
Themed Content: Role of Environmental Stressors in the Developmental Origins of Disease
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 1: Including Themed Content: Role of Environmental Stressors in the Developmental Origins of Disease , 23 February 2011 , pp. 3 - 8
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Flegal, KM, Carroll, MD, Ogden, CL, et al. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010; 303, 235–241.CrossRefGoogle ScholarPubMed
2. World Health Organization Global Strategy on Diet, Physical Activity and Health: Obesity and Overweight. 2009; Retrieved 13 May 2010 from http://www.who.int/dietphysicalactivity/publications/facts/obesity/en/.Google Scholar
3.Grun, F, Blumberg, B. Endocrine disrupters as obesogens. Mol Cell Endocrinol. 2009; 304, 19–29.CrossRefGoogle ScholarPubMed
4.Grun, F, Blumberg, B. Minireview: the case for obesogens. Mol Endocrinol. 2009; 23, 1127–1134.CrossRefGoogle ScholarPubMed
5.Nyirenda, MJ, Lindsay, RS, Kenyon, CJ, et al. Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest. 1998; 101, 2174–2181.CrossRefGoogle ScholarPubMed
6.Achard, V, Boullu-Ciocca, S, Desbriere, R, et al. Perinatal programming of central obesity and the metabolic syndrome: role of glucocorticoids. Metab Syndr Relat Disord. 2006; 4, 129–137.CrossRefGoogle ScholarPubMed
7.Hales, CN, Barker, DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001; 60, 5–20.CrossRefGoogle ScholarPubMed
8.Barker, DJ, Osmond, C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986; 1, 1077–1081.CrossRefGoogle ScholarPubMed
9.Barker, DJ, Osmond, C. Low birth weight and hypertension. BMJ. 1988; 297, 134–135.CrossRefGoogle ScholarPubMed
10.Barker, DJ, Osmond, C, Golding, J, et al. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564–567.CrossRefGoogle ScholarPubMed
11.Power, C, Jefferis, BJ. Fetal environment and subsequent obesity: a study of maternal smoking. Int J Epidemiol. 2002; 31, 413–419.CrossRefGoogle ScholarPubMed
12.Baillie-Hamilton, PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med. 2002; 8, 185–192.CrossRefGoogle ScholarPubMed
13.Heindel, JJ. Endocrine disruptors and the obesity epidemic. Toxicol Sci. 2003; 76, 247–249.CrossRefGoogle ScholarPubMed
14.Badman, MK, Flier, JS. The gut and energy balance: visceral allies in the obesity wars. Science. 2005; 307, 1909–1914.CrossRefGoogle ScholarPubMed
15.Rangwala, SM, Lazar, MA. Transcriptional control of adipogenesis. Annu Rev Nutr. 2000; 20, 535–559.CrossRefGoogle ScholarPubMed
16.Evans, RM, Barish, GD, Wang, YX. PPARs and the complex journey to obesity. Nat Med. 2004; 10, 355–361.CrossRefGoogle ScholarPubMed
17.Lazar, MA. How obesity causes diabetes: not a tall tale. Science. 2005; 307, 373–375.CrossRefGoogle Scholar
18.Tontonoz, P, Spiegelman, BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem. 2008; 77, 289–312.CrossRefGoogle ScholarPubMed
19.Grun, F, Blumberg, B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006; 147, S50–S55.CrossRefGoogle ScholarPubMed
20.Grun, F, Watanabe, H, Zamanian, Z, et al. Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol Endocrinol. 2006; 20, 2141–2155.CrossRefGoogle ScholarPubMed
21.Newbold, RR, Padilla-Banks, E, Snyder, RJ, et al. Developmental exposure to estrogenic compounds and obesity. Birth Defects Res A Clin Mol Teratol. 2005; 73, 478–480.CrossRefGoogle ScholarPubMed
22.Newbold, RR, Padilla-Banks, E, Jefferson, WN. Environmental estrogens and obesity. Mol Cell Endocrinol. 2009; 304, 84–89.CrossRefGoogle ScholarPubMed
23.Rubin, BS, Murray, MK, Damassa, DA, et al. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ Health Perspect. 2001; 109, 675–680.CrossRefGoogle ScholarPubMed
24.Larsen, TM, Toubro, S, Astrup, A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord. 2003; 27, 147–161.CrossRefGoogle ScholarPubMed
25.Rubenstrunk, A, Hanf, R, Hum, DW, et al. Safety issues and prospects for future generations of PPAR modulators. Biochim Biophys Acta. 2007; 1771, 1065–1081.CrossRefGoogle ScholarPubMed
26.Stahlhut, RW, van Wijgaarden, E, Dye, TD, et al. Concentrations of urinary phthalate metabolites are associated with increased waist circumferece and insulin resistance in adult U.S. males. Environ Health Perspect. 2007; 115, 876–882.CrossRefGoogle ScholarPubMed
27.Hurst, CH, Waxman, DJ. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci. 2003; 74, 297–308.CrossRefGoogle ScholarPubMed
28.Feige, JN, Gelman, L, Rossi, D, et al. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J Biol Chem. 2007; 282, 19152–19166.CrossRefGoogle ScholarPubMed
29.Hines, EP, White, SS, Stanko, JP, et al. Phenotypic dichotomy following developmental exposure to perfluorooctanoic acid (PFOA) in female CD-1 mice: low doses induce elevated serum leptin and insulin, and overweight in mid-life. Mol Cell Endocrinol. 2009; 304, 97–105.CrossRefGoogle ScholarPubMed
30.Inadera, H, Shimomura, A. Environmental chemical tributyltin augments adipocyte differentiation. Toxicol Lett. 2005; 159, 226–234.CrossRefGoogle ScholarPubMed
31.Kanayama, T, Kobayashi, N, Mamiya, S, et al. Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway. Mol Pharmacol. 2005; 67, 766–774.CrossRefGoogle ScholarPubMed
32.Carfi, M, Croera, C, Ferrario, D, et al. TBTC induces adipocyte differentiation in human bone marrow long term culture. Toxicology. 2008; 249, 11–18.CrossRefGoogle ScholarPubMed
33.Blaber, SJM. The occurrence of a penis-like outgrowth behind the right tentacle in spent females of Nucella lapillus. Proc Malacol Soc Lon. 1970; 39, 231–233.Google Scholar
34.Gibbs, P, Bryan, G. Reproductive failure in populations of the dog-whelk, Nucella lapillus, caused by imposex induced by tributyltin from antifouling paints. J Mar Biol Assoc U.K. 1986; 66, 767–777.CrossRefGoogle Scholar
35.Shimasaki, Y, Kitano, T, Oshima, Y, et al. Tributyltin causes masculinization in fish. Environ Toxicol Chem. 2003; 22, 141–144.CrossRefGoogle ScholarPubMed
36.Kirchner, S, Kieu, T, Chow, C, et al. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol Endocrinol. 2010; 24, 526–539.CrossRefGoogle Scholar
37.Kannan, K, Senthilkumar, K, Giesy, J. Occurrence of butyltin compounds in human blood. Environ Sci Technol. 1999; 33, 1776–1779.CrossRefGoogle Scholar
38.Rantakokko, P, Turunen, A, Verkasalo, PK, et al. Blood levels of organotin compounds and their relation to fish consumption in Finland. Sci Total Environ. 2008; 399, 90–95.CrossRefGoogle ScholarPubMed
39.Anastas, P, Eghbali, N. Green chemistry: principles and practice. Chem Soc Rev. 2010; 39, 301–312.CrossRefGoogle ScholarPubMed