Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males

Stahlhut, Richard W.; Wijngaarden, Edwin van; Dye, Timothy D.; Cook, Stephen; Swan, Shanna H.

doi:10.1289/ehp.9882

Cited by 571 publications

(393 citation statements)

References 68 publications

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“…Finally, we showed that DEHP dose-dependently induce the expression of the CAR target gene CYP2B6 in primary human hepatocytes. This original finding is discussed in view of the crucial role played by the liver in controlling energy homeostasis and the recent findings which associate phthalate exposure to the onset of the metabolic syndrome in men [18,19].…”

Section: Introductionmentioning

confidence: 91%

“…In mammals, including humans, phthalate exposure is associated with endocrine disruption [15][16][17] and metabolic disorders [18,19]. In rodents, in utero exposure to phthalates results in developmental and reproductive defects similar to those termed testicular dysgenesis syndrome in humans [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, two independent cross sectional studies of the National Health And Nutrition Examination Survey [NHANES, 1999[NHANES, -2002 have provided consistent conclusions which associate several urinary phthalates metabolites with key features of the metabolic syndrome (body mass index, abdominal adiposity and insulin resistance) [18,19]. Based on several studies, it has been suggested that the onset of the metabolic syndrome could be favoured by prolonged exposure to low concentrations of environmental pollutants, including phthalates, which are collectively referred to as environmental obesogens [18,26,27].…”

Section: Introductionmentioning

confidence: 99%

“…Based on several studies, it has been suggested that the onset of the metabolic syndrome could be favoured by prolonged exposure to low concentrations of environmental pollutants, including phthalates, which are collectively referred to as environmental obesogens [18,26,27]. However, the mechanisms involved in these new aspects of phthalate metabolic impact remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): A novel signalling pathway sensitive to phthalates

Eveillard¹,

Mselli-Lakhal²,

Mogha³

et al. 2009

Biochemical Pharmacology

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To cite this version:Alexandre Eveillard, Laïla Mselli-Lakhal, Ariane Mogha, Frédéric Lasserre, Arnaud Polizzi, et al.. Di-(2-ethylhexyl)-phthalate (DEHP) activates the Constitutive Androstane Receptor (CAR): a novel signalling pathway sensitive to phthalates. Biochemical Pharmacology, Elsevier, 2009, 77 (11) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 This finding demonstrates that CAR also represents a transcriptional regulator sensitive to phthalates. CAR-mediated effects of DEHP provide a new rationale for most endpoints of phthalates toxicity described previously, including endocrine disruption, hepatocarcinogenesis and the metabolic syndrome.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): A novel signalling pathway sensitive to phthalates

Eveillard¹,

Mselli-Lakhal²,

Mogha³

et al. 2009

Biochemical Pharmacology

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“…In short-and long-term rodent studies, dose-related adverse effects, such as deregulated levels of serum insulin, blood glucose, liver glycogen, T3, T4 and thyroid stimulating hormone as well as cortisol, were observed. 19,20 Even more specifically, Stahlhut et al 21 showed that the log-transformed concentrations of several phthalate metabolites positively correlated with abdominal obesity and insulin resistance in adult US males.…”

Section: Phthalates and Metabolic Disruptionmentioning

confidence: 99%

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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