title: Estrogen sulfotransferase inhibits adipocyte differentiation.
abstract: The estrogen sulfotransferase (EST) is a phase II drug-metabolizing enzyme known to catalyze the sulfoconjugation of estrogens. EST is highly expressed in the white adipose tissue of male mice, but the role of EST in the development and function of adipocytes remains largely unknown. In this report, we showed that EST played an important role in adipocyte differentiation. EST was highly expressed in 3T3-L1 preadipocytes and primary mouse preadipocytes. The expression of EST was dramatically reduced in differentiated 3T3-L1 cells and mature primary adipocytes. Overexpression of EST in 3T3-L1 cells prevented adipocyte differentiation. In contrast, preadipocytes isolated from EST knockout (EST-/-) mice exhibited enhanced differentiation. The inhibitory effect of EST on adipogenesis likely resulted from the sustained activation of ERK1/2 MAPK and inhibition of insulin signaling, leading to a failure of switch from clonal expansion to differentiation. The enzymatic activity of EST was required for the inhibitory effect of EST on adipogenesis, because an enzyme-dead EST mutant failed to inhibit adipocyte differentiation. In vivo, overexpression of EST in the adipose tissue of female transgenic mice resulted in smaller adipocyte size. Taken together, our results suggest that EST functions as a negative regulator of adipogenesis.
authors.affiliation: Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Taira
authors.initials: T
authors.lastname: Wada
authors.forename: Chibueze A
authors.initials: CA
authors.lastname: Ihunnah
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chai
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Philips
authors.forename: J Peter
authors.initials: JP
authors.lastname: Rubin
authors.forename: Kacey G
authors.initials: KG
authors.lastname: Marra
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D048429:Cell Size / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases; D015238:Sulfotransferases; C020122:estrone sulfotransferase