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

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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.

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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

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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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  1. Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, USA

    Felix Grün & Bruce Blumberg

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Grün, F., Blumberg, B. Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev Endocr Metab Disord 8, 161–171 (2007). https://doi.org/10.1007/s11154-007-9049-x

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