Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes.
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.


OBJECTIVE
In this study we aimed to compare a) the effects of low doses of BPA and estradiol (E(2)) 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) alpha and beta, G-protein-coupled receptor 30 (GPR30), and ERRs alpha, beta, and gamma 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 E(2). Adipose tissue expresses similar mRNA levels of ERalpha, ERbeta, and ERRgamma, and 20- to 30-fold lower levels of GPR30, ERRalpha, and ERRbeta.


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.
Hugo
Eric R
ER
Department of Cell and Cancer Biology, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH 45267, USA.
Brandebourg
Terry D
TD
Woo
Jessica G
JG
Loftus
Jean
J
Alexander
J Wesley
JW
Ben-Jonathan
Nira
N
D052242:Adiponectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D001559:Benzhydryl Compounds; D017931:DNA Primers; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
D052242:Adiponectin; D001559:Benzhydryl Compounds; D017931:DNA Primers; D052244:Endocrine Disruptors; D004958:Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds