Effects of bisphenol A on adipokine release from human adipose tissue: Implications for the metabolic syndrome

Abstract

Bisphenol A (BPA) is one of the most prevalent and best studied endocrine disruptors. After years of exposure to consumer products containing BPA, most individuals tested have circulating BPA at the low nanomolar levels. In addition to its well documented actions on the reproductive system, BPA exerts a wide variety of metabolic effects. This review summarizes recent findings on the ability of BPA, at environmentally relevant doses, to inhibit adiponectin and stimulate the release of inflammatory adipokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) from human adipose tissue. Expression of several classical and non-classical estrogen receptors in human adipose tissue raises the possibility of their involvement as mediators of BPA actions. The implications of these observations to the obesity-related metabolic syndrome and its sequelae are discussed.

Fig 1

Structures of bisphenol A (BPA) and related compounds: estradiol (E2), polycarbonates, diethylstilbestrol (DES), and bisphenol A diglycidyl ether (BADGE).

Fig 2

Comparison of the effects of BPA (B), estradiol (E), and ICI (I) on adipokine release from human adipose tissue explants. Upper left panel: Dose-dependent effects of BPA on adiponectin release from a representative patient (Means±SEM of 5 replicates). All other panels show release as percent of control (C). Values are means±SEM; N = 4 patients. Subcutaneous adipose tissue explants, obtained from patients undergoing abdominoplasty, were incubated for 6 hrs with the various compounds. Conditioned media were analyzed for adiponectin, interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) by their respective ELISAs. * designates significant difference from controls (P<0.05).

Fig 3

Relative expression of classical and non-classical estrogen receptors in human visceral adipose tissue, as determined by real-time PCR. Values are presented as percent of ERα expression on a logarithmic scale to highlight low abundance receptors. ERα/β-estrogen receptor α or β; GPR30 - G-protein coupled receptor 30; ERRα/β/γ - estrogen related receptor α, β, or γ. (Redrawn and modified from Hugo et al. 2008).

Fig 4

A model depicting an integrated view of the various factors that affect the obesity-related metabolic syndrome. BPA suppresses adiponectin and stimulates inflammatory cytokines by acting on adipocytes and infiltrating macrophages. Adiponectin is an insulin sensitizer whereas cytokines such as IL-6 and TNFα promote insulin resistance. The opposing actions of BPA on these adipokines contribute to the development and manifestation of the metabolic syndrome.