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

Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N - Environ. Health Perspect. (2008)

Bottom Line: 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.BPA at environmentally relevant doses inhibits the release of a key adipokine that protects humans from metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Cancer Biology, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH 45267, 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 (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.

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Related in: MedlinePlus

Depot-specific differences in the expression of putative receptors that may mediate the action of BPA or E2, as determined by real-time reverse transcriptase PCR. (A) Differences in expression of ERα, ERβ, GPR30, ERRα, ERRβ, and ERRγ in SC and breast (BR) adipose tissue calculated as fold change (shown above bars) relative to VIS adipose tissue. (B) Relative abundance of the above receptors in VIS adipose tissue compared with ERαexpression.
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f5-ehp-116-1642: Depot-specific differences in the expression of putative receptors that may mediate the action of BPA or E2, as determined by real-time reverse transcriptase PCR. (A) Differences in expression of ERα, ERβ, GPR30, ERRα, ERRβ, and ERRγ in SC and breast (BR) adipose tissue calculated as fold change (shown above bars) relative to VIS adipose tissue. (B) Relative abundance of the above receptors in VIS adipose tissue compared with ERαexpression.

Mentions: We next examined breast, VIS, and SC adipose tissue, each pooled from four or five women, for expression of putative receptors that may mediate the actions of BPA and/or E2. Figure 5A shows relative mRNA expression of ERα, ERβ, GPR30, ERRα, ERRβ, and ERRγ in breast and SC adipose tissue, compared with VIS adipose tissue, which was used as a reference. All six receptors were more highly expressed in breast adipose tissue (from 1.8- to 7.3-fold) than VIS adipose tissue. The expression of GPR30 and ERRα was approximately the same in VIS and SC adipose tissue (1.4- to 1.5-fold), whereas ERα, ERβ, and ERRβ were moderately higher (from 1.7- to 2.1-fold) in SC tissue. Notably, expression of ERRγ was much lower (0.3-fold) in SC than in VIS adipose tissue.


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

Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N - Environ. Health Perspect. (2008)

Depot-specific differences in the expression of putative receptors that may mediate the action of BPA or E2, as determined by real-time reverse transcriptase PCR. (A) Differences in expression of ERα, ERβ, GPR30, ERRα, ERRβ, and ERRγ in SC and breast (BR) adipose tissue calculated as fold change (shown above bars) relative to VIS adipose tissue. (B) Relative abundance of the above receptors in VIS adipose tissue compared with ERαexpression.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2599757&req=5

f5-ehp-116-1642: Depot-specific differences in the expression of putative receptors that may mediate the action of BPA or E2, as determined by real-time reverse transcriptase PCR. (A) Differences in expression of ERα, ERβ, GPR30, ERRα, ERRβ, and ERRγ in SC and breast (BR) adipose tissue calculated as fold change (shown above bars) relative to VIS adipose tissue. (B) Relative abundance of the above receptors in VIS adipose tissue compared with ERαexpression.
Mentions: We next examined breast, VIS, and SC adipose tissue, each pooled from four or five women, for expression of putative receptors that may mediate the actions of BPA and/or E2. Figure 5A shows relative mRNA expression of ERα, ERβ, GPR30, ERRα, ERRβ, and ERRγ in breast and SC adipose tissue, compared with VIS adipose tissue, which was used as a reference. All six receptors were more highly expressed in breast adipose tissue (from 1.8- to 7.3-fold) than VIS adipose tissue. The expression of GPR30 and ERRα was approximately the same in VIS and SC adipose tissue (1.4- to 1.5-fold), whereas ERα, ERβ, and ERRβ were moderately higher (from 1.7- to 2.1-fold) in SC tissue. Notably, expression of ERRγ was much lower (0.3-fold) in SC than in VIS adipose tissue.

Bottom Line: 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.BPA at environmentally relevant doses inhibits the release of a key adipokine that protects humans from metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Cancer Biology, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH 45267, 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 (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.

Show MeSH
Related in: MedlinePlus