Bisphenol A downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes.
OBJECTIVE
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 (20-80 microM) in serum-deprived medium. The medium was filtered through a 0.2 microm 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 80 microM BPA were analyzed by Western blot.


RESULTS
The control cultures (i.e., BPA was absent during a 24-h treatment period) contained 49.4 microg/mg DNA of adiponectin in the cells and secreted 35.5 microg/mg DNA of adiponectin into the medium. BPA at 80 microM 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.
Kidani
Teruki
T
Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Iyo-gun, Ehime, Japan.
Kamei
Setsuya
S
Miyawaki
Joji
J
Aizawa
Junichi
J
Sakayama
Kenshi
K
Masuno
Hiroshi
H
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001559:Benzhydryl Compounds; D015153:Blotting, Western; D015536:Down-Regulation; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D020738:Leptin / Q000378:metabolism; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000098923:Bisphenol B Compounds; D000098826:Bisphenol A Compounds
D052242:Adiponectin; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D020738:Leptin; D010636:Phenols; D051057:Proto-Oncogene Proteins c-akt; C492482:bisphenol B; D000098923:Bisphenol B Compounds; C006780:bisphenol A; D000098826:Bisphenol A Compounds