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Eric R. Hugo,¹ Terry D. Brandebourg,¹ Jessica G. Woo,² Jean Loftus,³ J. Wesley Alexander,⁴ and Nira Ben-Jonathan¹

¹Department of Cell and Cancer Biology, University of Cincinnati, Cincinnati, Ohio, USA; ²Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; ³Christ Hospital, Cincinnati, Ohio, USA; ⁴Center for Surgical Weight Loss, University of Cincinnati, Cincinnati, Ohio, USA

Abstract
Background: The incidence of obesity has risen dramatically over the last few decades. This epidemic may be affected by exposure to xenobiotic chemicals. Bisphenol A (BPA) , an endocrine disruptor, is detectable at nanomolar levels in human serum worldwide. Adiponectin is an adipocyte-specific hormone that increases insulin sensitivity and reduces tissue inflammation. Thus, any factor that suppresses adiponectin release could lead to insulin resistance and increased susceptibility to obesity-associated diseases.

Objectives: In this study we aimed to compare a) the effects of low doses of BPA and estradiol (E₂) on adiponectin secretion from human breast, subcutaneous, and visceral adipose explants and mature adipocytes, and b) expression of putative estrogen and estrogen-related receptors (ERRs) in these tissues.

Methods: We determined adiponectin levels in conditioned media from adipose explants or adipocytes by enzyme-linked immunosorbant assay. We determined expression of estrogen receptors (ERs) α and β, G-protein–coupled receptor 30 (GPR30) , and ERRs α, β, and γ by quantitative real-time polymerase chain reaction.

Results: BPA at 0.1 and 1 nM doses suppressed adiponectin release from all adipose depots examined. Despite substantial variability among patients, BPA was as effective, and often more effective, than equimolar concentrations of E₂. Adipose tissue expresses similar mRNA levels of ERα, ERβ, and ERRγ, and 20- to 30-fold lower levels of GPR30, ERRα, and ERRβ.

Conclusions: BPA at environmentally relevant doses inhibits the release of a key adipokine that protects humans from metabolic syndrome. The mechanism by which BPA suppresses adiponectin and the receptors involved remains to be determined.

Key words: adipocytes, adiponectin, bisphenol A, estradiol, estrogen receptors, estrogen-related receptors, human adipose explants, obesity. Environ Health Perspect 116: 1642–1647 (2008) .  doi:10.1289/ehp.11537 available via http://dx.doi.org/ [Online 14 August 2008]

Address correspondence to N. Ben-Jonathan, Department of Cell and Cancer Biology, University of Cincinnati, 3125 Eden Ave., Cincinnati, OH 45267-0521 USA. Telephone: (513) 558-4821. Fax: (513) 558-4823. E-mail: Nira.Ben-Jonathan@uc.edu

This work was supported by National Institutes of Health (NIH) grants ES012212, ES016803, and CA096613 ; Department of Defense grant BC05725 ; Susan G. Komen Breast Cancer Foundation grant BCRT87406 (N.B.J.) ; and NIH Center for Environmental Genetics P30 ES06096 (N.B.J., J.G.W.) .

The authors declare they have no competing financial interests.

Received 3 April 2008 ; accepted 14 August 2008.