Estrogenic chemicals at body burden levels attenuate energy metabolism in 3T3-L1 adipocytes

The study aimed to examine effects of environmental estrogens at body burden levels on energy metabolism in fat cells. Acclimation of T47D-KBluc cells in estrogen-deprived medium was established for high performance of estrogen-responsive luciferase reporter assay. With the assay, relative estrogenic potency of four selected estrogen receptor (ER) agonists, i.e. diethylstilbestrol, β-estradiol, 4-nonylphenol and bisphenol A, were determined. Immunoblot analysis revealed that the ER agonists at both EC80 and EC100 caused rapid and transient phosphorylation of extracellular signal-regulated kinases (ERK) in an ER-dependent manner. 3T3-L1 adipocytes treated with the ER agonists at EC80 for 24 hours exhibited significant downregulation in mitochondrial respiration and glycolytic function. Importantly, EC80 values of 4-nonylphenol (6.0 × 10−10 m) and bisphenol A (1.0 × 10−8 m) are in the range of human body burdens. The finding that estrogenic chemicals at body burden levels cause significant impact on fat cell energy metabolism raises an important public health issue that deserves more attention.