PMID- 25047013 OWN - NLM STAT- MEDLINE DCOM- 20150824 LR - 20181202 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 22 IP - 11 DP - 2014 Nov TI - Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. PG - 2333-43 LID - 10.1002/oby.20848 [doi] AB - OBJECTIVE: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and adipogenesis of human preadipocytes. However, the mechanism of action of BPA-induced human adipogenesis remains to be determined. METHODS: Primary human preadipocytes were differentiated in the presence of 50 microM BPA or 1 microM dexamethasone (DEX) for 48 hours. Potential mechanisms of BPA-induced adipogenesis were evaluated using gene expression microarray analysis. RESULTS: Microarray analysis revealed 373 differentially expressed genes following BPA treatment, including upregulation of sterol regulatory element binding factor 1 (SREBF1), a key regulator of lipid metabolism. For DEX-treated preadipocytes, 2167 genes were differentially expressed, including upregulation of the adipogenic marker lipoprotein lipase. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX. BPA exposure was associated with expression changes in the genes involved in triacylglycerol accumulation while DEX was linked to triacylglycerol and fatty acid metabolism. The analysis also revealed enrichment of genes following BPA exposure in the thyroid-receptor/retinoic X receptor (TR/RXR) and mammalian target of rapamycin (mTOR) signaling pathways. CONCLUSIONS: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR, and the mTOR pathways. CI - (c) 2014 The Obesity Society. FAU - Boucher, Jonathan G AU - Boucher JG AD - In Vitro Molecular Toxicology Laboratory, Environmental Health Science and Research Bureau, Health Canada, Ottawa, Canada. FAU - Husain, Mainul AU - Husain M FAU - Rowan-Carroll, Andrea AU - Rowan-Carroll A FAU - Williams, Andrew AU - Williams A FAU - Yauk, Carole L AU - Yauk CL FAU - Atlas, Ella AU - Atlas E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140722 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Benzhydryl Compounds) RN - 0 (Phenols) RN - 0 (Triglycerides) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 3.1.1.34 (Lipoprotein Lipase) RN - MLT3645I99 (bisphenol A) SB - IM MH - Adipocytes/*drug effects/physiology MH - Adipogenesis/drug effects/genetics MH - Benzhydryl Compounds/*pharmacology MH - Cell Differentiation/*drug effects/genetics MH - Cells, Cultured MH - Dexamethasone/pharmacology MH - *Gene Expression Profiling MH - Gene Expression Regulation/*drug effects MH - Humans MH - Lipid Metabolism/genetics MH - Lipoprotein Lipase/metabolism MH - Microarray Analysis MH - Obesity/genetics/metabolism/pathology MH - Phenols/*pharmacology MH - Signal Transduction/genetics MH - Triglycerides/metabolism EDAT- 2014/07/23 06:00 MHDA- 2015/08/25 06:00 CRDT- 2014/07/23 06:00 PHST- 2014/04/28 00:00 [received] PHST- 2014/07/09 00:00 [accepted] PHST- 2014/07/23 06:00 [entrez] PHST- 2014/07/23 06:00 [pubmed] PHST- 2015/08/25 06:00 [medline] AID - 10.1002/oby.20848 [doi] PST - ppublish SO - Obesity (Silver Spring). 2014 Nov;22(11):2333-43. doi: 10.1002/oby.20848. Epub 2014 Jul 22.