Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates

Grün, Felix; Watanabe, Hidenobu; Zamanian, Zahra; Maeda, Lauren S.; Arima, Kayo; Cubacha, Ryan; Gardiner, David M.; Kanno, Jun; Iguchi, Taisen; Blumberg, Bruce

doi:10.1210/me.2005-0367

Cited by 554 publications

(525 citation statements)

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“…With regard to the role of EDC exposure in utero, the correlation between prenatal maternal smoking and higher prevalence of obesity reported in a British adult population represents a proof-ofconcept. 11,12 Along this line, Grun et al 13 showed that organotins, a group of diverse and widely distributed environmental pollutants, promote adipogenesis in mouse models, with embryonic development representing a particularly critical period of exposure. These in vivo results support the Barker's hypothesis, 14 which postulates that in utero fetal nutritional status is a potential risk factor for metabolic diseases.…”

Section: Edcs and Obesitymentioning

confidence: 99%

“…Indeed, PPARa is a recognized target for pollutants as it mediates peroxisome proliferation and associated carcinogenic effects in rodent liver in response to a class of chemicals referred to as peroxisome proliferator chemicals. In addition, several reports have showed PPAR activation by environmental pollutants such as phthalates produced by the plastic industry, [38][39][40] perfluorooctane-based chemicals found in industrial surfactants, 41,42 organotins used as agricultural fungicides and anti-fouling agents in ship paints, 13,43 as well as several other pesticides. 44,45 However, fairly little is known on the metabolic consequences of PPAR activation by pollutants, both in terms of molecular mechanism of action and physiological outputs.…”

Section: The Nuclear Receptor Superfamily and Endocrine Disruptionmentioning

confidence: 99%

“…Therefore, a long-term PPARg activation by agonists, such as pharmaceutical therapies for type 2 diabetes, may promote weight gain as a side effect because of increased fat storage due to the induction of the 'thrifty gene response'. 33 In a recent study, Grün et al 13 showed that organotins, such as Tributyltin chloride (TBT) and bis(triphenyltin) oxide, phenocopy the effects of PPARg and RXR ligands. Firstly, they describe in vitro that TBT, although structurally distinct from described ligands, binds to and activates the three human subtypes of RXR as well many permissive heterodimeric partners such as the liver X receptor, PPARb, nuclear receptor related-1 and PPARg, but not PPARa.…”

Section: Pparc and Organotins: Edcs' Effects On Obesitymentioning

confidence: 99%

“…Consistent with the critical role played by PPARg-RXR signaling in mammalian adipogenesis, TBT induced adipocyte differentiation by direct transcriptional effects on PPARg target genes. 13 The authors further showed that TBT is a Phthalate bound to PPARs create metabolic interference C Casals-Casas et al potential adipogenic agent in vivo that induces lipogenic PPARg-RXR target gene expression in liver and adipose tissue, and modulates factors associated with early adipocyte differentiation. Finally, they showed in mouse models that in utero exposure to TBT causes a disorganization of hepatic and gonadal architecture, some steatosis in liver, and an increase of lipid accumulation and mature adipocytes.…”

Section: Pparc and Organotins: Edcs' Effects On Obesitymentioning

confidence: 99%

“…On the basis of similar adipogenic activity of phthalates and organotins, 13 we reasoned that phthalates could have actions on adipogenesis and fat accretion in vivo. Earlier studies have indeed shown that both in utero and adult exposure to phthalates have various effects on endocrine functions, in some cases mediated by PPARs.…”

Section: Pparc and Phthalates: Stepping In With The Definition Of A Smentioning

confidence: 99%

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Interference of pollutants with PPARs: endocrine disruption meets metabolism

2008

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The concept of endocrine disruption emerged over a decade ago with the observation that several natural or industrial compounds can interfere with estrogen and androgen signaling, and thereby affect both male and female reproductive functions. Since then, many endocrine-disrupting chemicals (EDCs) have been identified and the concept has been broadened to receptors regulating other aspects of endocrine pathways. In that context, interference of EDCs with receptors regulating metabolism has been proposed as a factor that could contribute to metabolic diseases such as obesity and diabetes. We review recent studies showing that several pollutants, including phthalates and organotins, interfere with PPAR (peroxisome proliferator-activated receptors) nuclear receptors and may thereby affect metabolic homeostasis. Particular emphasis is given on the mechanisms of action of these compounds. However, unlike what has been suspected, we provide evidence from mouse models suggesting that in utero exposure to the phthalate ester di-ethyl-hexyl-phthalate most likely does not predispose to obesity. Collectively, these studies define a subclass of EDCs that perturb metabolic signaling and that we propose to define as metabolic disruptors.

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Section: Edcs and Obesitymentioning

confidence: 99%

Section: The Nuclear Receptor Superfamily and Endocrine Disruptionmentioning

confidence: 99%

Section: Pparc and Organotins: Edcs' Effects On Obesitymentioning

confidence: 99%

Section: Pparc and Organotins: Edcs' Effects On Obesitymentioning

confidence: 99%

Section: Pparc and Phthalates: Stepping In With The Definition Of A Smentioning

confidence: 99%

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Interference of pollutants with PPARs: endocrine disruption meets metabolism

2008

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Combinatorial pathway disruption is a powerful approach to delineate metabolic impacts of endocrine disruptors

et al. 2022

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The prevalence of metabolic diseases, such as obesity, diabetes, metabolic syndrome and chronic liver diseases among others, has been rising for several years. Epidemiology and mechanistic (in vivo, in vitro and in silico) toxicology have recently provided compelling evidence implicating the chemical environment in the pathogenesis of these diseases. In this review, we will describe the biological processes that contribute to the development of metabolic diseases targeted by metabolic disruptors, and will propose an integrated pathophysiological vision of their effects on several organs. With regard to these pathomechanisms, we will discuss the needs, and the stakes of evolving the testing and assessment of endocrine disruptors to improve the prevention and management of metabolic diseases that have become a global epidemic since the end of last century.

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