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Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis

  • Felix Grün
  • Bruce Blumberg
Article

Abstract

The modern world is plagued with expanding epidemics of diseases related to metabolic dysfunction. The factors that are driving obesity, diabetes, cardiovascular disease, hypertension, and dyslipidemias (collectively termed metabolic syndrome) are usually ascribed to a mismatch between the body’s homeostatic nutrient requirements and dietary excess, coupled with insufficient exercise. The environmental obesogen hypothesis proposes that exposure to a toxic chemical burden is superimposed on these conditions to initiate or exacerbate the development of obesity and its associated health consequences. Recent studies have proposed a first set of candidate obesogens (diethylstilbestrol, bisphenol A, phthalates and organotins among others) that target nuclear hormone receptor signaling pathways (sex steroid, RXR–PPARγ and GR) with relevance to adipocyte biology and the developmental origins of health and disease (DOHaD). Perturbed nuclear receptor signaling can alter adipocyte proliferation, differentiation or modulate systemic homeostatic controls, leading to long-term consequences that may be magnified if disruption occurs during sensitive periods during fetal or early childhood development.

Keywords

Environmental obesogen Metabolic syndrome Nuclear hormone receptors RXR PPARγ Organotin Obesogen 

Abbreviations

RXR

retinoic X receptor

PPARγ

peroxisome proliferatpr activated receptor gamma

LXR

liver X receptor

FXR

farnesoid X receptor

GR

glucocorticoid receptor

ER

estrogen receptor

BPA

bisphenol A

DES

diethylstilbestrol

TBT

tributyltin chloride

TPT

triphenyltin chloride

EDC

endocrine disrupting chemicals

TZD

thiazolidinedione

Notes

Acknowledgements

Research in the authors laboratory was supported by grants from the US Environmental Protection Agency (STAR R830686) and National Institutes of Health (GM-60572) (to B.B.) and from the University of California Toxic Substance Research and Training Program (UC-37579) (to F.G.).

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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Developmental and Cell BiologyUniversity of California IrvineIrvineUSA

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