Adipocytes
Bisphenol A at Environmentally Relevant Doses Inhibits Adiponectin Release from Human Adipose Tissue Explants and Adipocytes
15/09/2008
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 nM levels in human serum worldwide. Adiponectin is an
adipocyte-specific hormone which increases insulin sensitivity and reduces tissue inflammation.
Thus, any factor which suppresses adiponectin release could lead to insulin resistance and
increased susceptibility to obesity-associated diseases.
Objectives: To compare: a) the effects of low doses of BPA and estradiol (E2) on adiponectin
secretion from human breast, subcutaneous (sc) and visceral (vis) adipose explants and mature
adipocytes, and b) expression of putative estrogen and estrogen-related receptors in these tissues.
Methods: Adiponectin levels in conditioned media (CM) from adipose explants or adipocytes
were determined by enzyme-linked immunosorbant assay (ELISA). Expression of estrogen
receptors (ER) α and β, G-protein-coupled receptor 30 (GPR30), and estrogen-related receptors
(ERR) α, β and γ was determined by quantitative real-time PCR.
Results: BPA at 0.1 and 1 nM doses suppressed adiponectin release from all adipose depots
examined. In spite of a 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 20-30 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 the metabolic syndrome. The mechanism by which BPA suppresses
adiponectin and the receptors involved remain to be determined.
Environ Health Perspect doi:10.1289/ehp.11537 available via http://dx.doi.org/ [Online 14 August 2008]
epidemic may be affected by exposure to xenobiotic chemicals. Bisphenol A (BPA), an
endocrine disruptor, is detectable at nM levels in human serum worldwide. Adiponectin is an
adipocyte-specific hormone which increases insulin sensitivity and reduces tissue inflammation.
Thus, any factor which suppresses adiponectin release could lead to insulin resistance and
increased susceptibility to obesity-associated diseases.
Objectives: To compare: a) the effects of low doses of BPA and estradiol (E2) on adiponectin
secretion from human breast, subcutaneous (sc) and visceral (vis) adipose explants and mature
adipocytes, and b) expression of putative estrogen and estrogen-related receptors in these tissues.
Methods: Adiponectin levels in conditioned media (CM) from adipose explants or adipocytes
were determined by enzyme-linked immunosorbant assay (ELISA). Expression of estrogen
receptors (ER) α and β, G-protein-coupled receptor 30 (GPR30), and estrogen-related receptors
(ERR) α, β and γ was determined by quantitative real-time PCR.
Results: BPA at 0.1 and 1 nM doses suppressed adiponectin release from all adipose depots
examined. In spite of a 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 20-30 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 the metabolic syndrome. The mechanism by which BPA suppresses
adiponectin and the receptors involved remain to be determined.
Environ Health Perspect doi:10.1289/ehp.11537 available via http://dx.doi.org/ [Online 14 August 2008]
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