Bisphenol A Downregulates Akt Signaling and Inhibits Adiponectin Production and Secretion in 3T3-L1 Adipocytes

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 17; no. 8; pp. 834 - 843
• Main Authors: Kidani, Teruki, Kamei, Setsuya, Miyawaki, Joji, Aizawa, Junichi, Sakayama, Kenshi, Masuno, Hiroshi
• Format: Journal Article
• Language: English
• Published: Japan Japan Atherosclerosis Society 01.01.2010
• Subjects: 3T3-L1 adipocytes; 3T3-L1 Cells; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adiponectin; Adiponectin - antagonists & inhibitors; Adiponectin - metabolism; Akt signaling; Animals; Benzhydryl Compounds; Bisphenol A; Blotting, Western; Down-Regulation; Estrogens, Non-Steroidal - pharmacology; Leptin - metabolism; Mice; Phenols - pharmacology; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.4051

Aim: The aim of this study was to investigate whether environmental endocrine-disrupting chemicals, bisphenol A (BPA) and BPA-related chemicals, affect adiponectin production and secretion in 3T3-L1 adipocytes and whether BPA acts through Akt signaling. Methods: 3T3-L1 adipocytes were treated for 24 h with BPA at various concentrations (20-80μM) in serum-deprived medium. The medium was filtered through a 0.2μm filter. Adiponectin in the infranatants of cell homogenates and in the media was measured using an adiponectin ELISA kit. The levels of Akt and p-Akt in cultures treated for 24 h with or without 80μM BPA were analyzed by Western blot. Results: The control cultures (i.e., BPA was absent during a 24-h treatment period) contained 49.4μg/mg DNA of adiponectin in the cells and secreted 35.5μg/mg DNA of adiponectin into the medium. BPA at 80μM dose-dependently decreased the amounts of intracellular and medium adiponectin by 60% (p<0.01) and 56% (p<0.01), respectively, and decreased the levels of Akt and p-Akt by 46% (p<0.01) and 29% (p<0.01), respectively, compared with the control cultures. Like BPA, bisphenol F (BPF), bisphenol E (BPE), and bisphenol B (BPB) decreased the amounts of intracellular and medium adiponectin. The order of the potential to decrease the amount of intracellular adiponectin was BPB>BPA>BPE>BPF. Conclusions: BPA downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes.