Environmental estrogens and obesity. Mol Cell Endocrinol

Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States.
Molecular and Cellular Endocrinology (Impact Factor: 4.41). 06/2009; 304(1-2):84-9. DOI: 10.1016/j.mce.2009.02.024
Source: PubMed


Many chemicals in the environment, in particular those with estrogenic activity, can disrupt the programming of endocrine signaling pathways that are established during development and result in adverse consequences that may not be apparent until much later in life. Most recently, obesity and diabetes join the growing list of adverse consequences that have been associated with developmental exposure to environmental estrogens during critical stages of differentiation. These diseases are quickly becoming significant public health issues and are fast reaching epidemic proportions worldwide. In this review, we summarize the literature from experimental animal studies documenting an association of environmental estrogens and the development of obesity, and further describe an animal model of exposure to diethylstilbestrol (DES) that has proven useful in studying mechanisms involved in abnormal programming of various differentiating estrogen-target tissues. Other examples of environmental estrogens including the phytoestrogen genistein and the environmental contaminant Bisphenol A are also discussed. Together, these data suggest new targets (i.e., adipocyte differentiation and molecular mechanisms involved in weight homeostasis) for abnormal programming by estrogenic chemicals, and provide evidence that support the scientific hypothesis termed "the developmental origins of adult disease". The proposal of an association of environmental estrogens with obesity and diabetes expands the focus on the diseases from intervention/treatment to include prevention/avoidance of chemical modifiers especially during critical windows of development.

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Available from: Wendy Jefferson, Jul 23, 2014
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    • "Despite from these numerous beneficial reports there are also concerns that ISOs, similar to other estrogenic compounds , promote fat accumulation and therefore consumption may be associated with an increased risk to develop obesity [15] [16] [17]. These concerns are in part based on the evidence that during critical periods of development estrogenic chemicals can have stimulatory effects on the development of obesity [18]. Obesogenic mechanisms were already discussed for xenoestrogens like bisphenol A [19] and diethylstilbestrol [20]. "
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    ABSTRACT: Scope: Traditional Asian diet rich in soy isoflavones (ISOs) is discussed to be linked to a lower obesity prevalence. In lifelong and short-term exposure scenarios we investigated effects of an ISO-rich diet on the body composition and development of obesity in female rats. Methods and results: Female Wistar rats grew up on ISO-free or ISO-rich control diet (CON ISO: 467 mg/kg diet). Starting postnatal day 83, ovariectomized and intact animals received high calorie Western diet (WD) in the absence or presence of ISO (WD ISO: 431 mg/kg diet) for 12 weeks to induce obesity or maintained on respective CON. One group starting ISO exposure after ovariectomy mimics short-term ISO exposure in postmenopausal Western women. Lifelong but not short-term ISO exposure resulted in reduced body weight, visceral fat mass, serum leptin and smaller adipocytes. ISO decreased hepatic SREBP-1c, ACC, FAS and PPARγ mRNA expression in non-obese animals. Moreover, ovariectomy reduced skeletal muscle weight, which was antagonized by both short-term and lifelong ISO exposure. Conclusion: Our results indicate that in female rats lifelong but not short-term ISO intake reduces the risk to develop obesity. Furthermore, lifelong and short-term ISO exposure may antagonize loss of skeletal muscle mass induced by ovariectomy. This article is protected by copyright. All rights reserved.
    Molecular Nutrition & Food Research 09/2015; DOI:10.1002/mnfr.201500240 · 4.60 Impact Factor
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    • "Increased incidence of breast cancer (Munoz-de-Toro et al., 2005), genital tract abnormalities (Skakkebaek et al., 1998), and fertility problems (Sharpe & Skakkebaek, 1993) are some of the most common abnormalities associated with early EDCs exposure. In addition, prenatal treatment with bisphenol-A (BPA) has been related to the development of obesity and diabetes (Heindel, 2003; Newbold et al., 2009; Alonso-Magdalena et al., 2010). In this review, we will analyze the experimental and epidemiological findings that point to BPA as an important risk factor in the adult origin of metabolic diseases. "
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    ABSTRACT: Obesity and type 2 diabetes mellitus (T2DM) are the most common metabolic disorders, with prevalence rates that are reaching epidemic proportions. Both are complex conditions affecting virtually all ages and with serious health consequences. The underlying cause of the problem is still puzzling, but both genetic and environmental factors including unhealthy diet, sedentary lifestyle, or the exposure to some environmental endocrine disrupting chemicals (EDCs) are thought to have a causal influence. In addition, the impact of early environment has recently emerged as an important factor responsible for the increased propensity to develop adult-onset metabolic disease. Suboptimal maternal nutrition during critical windows in fetal development is the most commonly studied factor affecting early programming of obesity and T2DM. In recent years, increasing experimental evidence shows that exposure to EDCs could also account for this phenomenon. In the present review, we will overview the most relevant findings that confirm the critical role of bisphenol-A, one of the most widespread EDCs, in the development of metabolic disorders.
    Dose-Response 06/2015; 13(2). DOI:10.1177/1559325815590395 · 1.22 Impact Factor
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    • "Several obesogenic chemicals have been identified in recent years , underscoring the rel - evance of this new model . Estrogenic EDCs such as diethylstilbestrol ( DES ) ( Newbold et al . , 2009"
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    ABSTRACT: Obesity and metabolic syndrome diseases have exploded into an epidemic of global proportions. The generally accepted cause of obesity is overconsumption of calorie-dense food and diminished physical activity (the calories in - calories out model). However, emerging evidence demonstrates that environmental factors can predispose exposed individuals to gain weight, irrespective of diet and exercise. The environmental obesogen model proposes that chemical exposure during critical stages in development can influence subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage. Numerous obesogens have been identified in recent years and some of these have been shown to act through the peroxisome proliferator activated receptor, the master regulator of adipogenesis. Others act through as yet unidentified pathways. Notably, some of these obesogens elicit transgenerational effects on a variety of health endpoints, including obesity in offspring after exposure of pregnant F0 females. Thus, prenatal exposure to xenobiotic compounds can have lasting, potentially permanent effects on the offspring of exposed animals. Transgenerational effects of chemical exposure raise the stakes in the debate about whether and how endocrine disrupting chemicals should be regulated.
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