Estrogen Sulfotransferase Inhibits Adipocyte Differentiation

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,...

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Veröffentlicht in:Molecular endocrinology (Baltimore, Md.) Md.), 2011-09, Vol.25 (9), p.1612-1623
Hauptverfasser: Wada, Taira, Ihunnah, Chibueze A, Gao, Jie, Chai, Xiaojuan, Zeng, Su, Philips, Brian J, Rubin, J. Peter, Marra, Kacey G, Xie, Wen
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container_issue 9
container_start_page 1612
container_title Molecular endocrinology (Baltimore, Md.)
container_volume 25
creator Wada, Taira
Ihunnah, Chibueze A
Gao, Jie
Chai, Xiaojuan
Zeng, Su
Philips, Brian J
Rubin, J. Peter
Marra, Kacey G
Xie, Wen
description 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.
doi_str_mv 10.1210/me.2011-1089
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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. 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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete
subjects 3T3-L1 Cells
Adipocytes - cytology
Adipocytes - drug effects
Adipocytes - enzymology
Adipogenesis - drug effects
Adipogenesis - genetics
Adipose Tissue - drug effects
Adipose Tissue - enzymology
Animals
Cell Differentiation - drug effects
Cell Differentiation - genetics
Cell Size - drug effects
Enzyme Activation - drug effects
Estradiol - pharmacology
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Gene Deletion
Gene Expression Regulation, Enzymologic - drug effects
Insulin - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Original Research
PPAR gamma - agonists
PPAR gamma - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction - drug effects
Sulfotransferases - genetics
Sulfotransferases - metabolism
title Estrogen Sulfotransferase Inhibits Adipocyte Differentiation
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