Dietary xenoestrogens differentially impair 3T3-L1 preadipocyte differentiation and persistently affect leptin synthesis.
Recent observations have highlighted adipogenesis alterations under exposure to several xenoestrogens at critical stages, and pointed at their possible involvement in the pathogenesis of obesity. However, it remains unclear whether these effects are mediated by classical estrogen receptor (ER) binding and subsequent transcriptional modulation. The aim of this study was to determine the (anti-)adipogenic impact of apigenin, bisphenol A, genistein and 17beta-estradiol at the onset of adipose cell maturation, and to correlate it to their estrogenic potential. In steroid-free conditions, 3T3-L1 preadipocytes were induced to differentiate in the presence of xenoestrogens for 2 days. DNA and triglyceride levels, leptin secretion and expression of Pref-1, C/EBPbeta, PPARgamma2, FAS, leptin and ERs were measured on days 0, 3 and 8 of differentiation. Genistein potently blocked mitotic clonal expansion and all markers of maturation. Bisphenol A and estradiol did not modify triglyceride accumulation but increased the expression of differentiation genes. Apigenin caused a weak but reversible delay in adipogenesis although it unexpectedly enhanced leptin synthesis. However, the expression of steroid hormone receptors was not associated with these differential effects. In conclusion, we could not put a clear estrogen-dependent mechanism forward, but early exposure to xenoestrogens persistently disrupted adipocyte gene expression and leptin synthesis.
Phrakonkham
Pascal
P
UMR1129 FLAVIC, INRA-ENESAD-Université de Bourgogne, F-21000 Dijon, France.
Viengchareun
Say
S
Belloir
Christine
C
Lombès
Marc
M
Artur
Yves
Y
Canivenc-Lavier
Marie-Chantal
MC
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D001559:Benzhydryl Compounds; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020738:Leptin / Q000096:biosynthesis*; D051379:Mice; D008954:Models, Biological; D047495:PPAR gamma / Q000235:genetics; D010636:Phenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000235:genetics; D000098826:Bisphenol A Compounds
D047310:Apigenin; D001559:Benzhydryl Compounds; D002135:Calcium-Binding Proteins; D004958:Estradiol; D004967:Estrogens; D019833:Genistein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D047495:PPAR gamma; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D019014:fas Receptor; C512925:Dlk1 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds