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 |
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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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Peter ; Marra, Kacey G ; Xie, Wen</creator><creatorcontrib>Wada, Taira ; Ihunnah, Chibueze A ; Gao, Jie ; Chai, Xiaojuan ; Zeng, Su ; Philips, Brian J ; Rubin, J. Peter ; Marra, Kacey G ; Xie, Wen</creatorcontrib><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.</description><identifier>ISSN: 0888-8809</identifier><identifier>EISSN: 1944-9917</identifier><identifier>DOI: 10.1210/me.2011-1089</identifier><identifier>PMID: 21816900</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>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</subject><ispartof>Molecular endocrinology (Baltimore, Md.), 2011-09, Vol.25 (9), p.1612-1623</ispartof><rights>Copyright © 2011 by The Endocrine Society</rights><rights>Copyright © 2011 by The Endocrine Society 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-eea7477a429cd9013ab7e1ac1e69dfaecf742fe8ee3704376f8a34c9adca56553</citedby><cites>FETCH-LOGICAL-c525t-eea7477a429cd9013ab7e1ac1e69dfaecf742fe8ee3704376f8a34c9adca56553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21816900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wada, Taira</creatorcontrib><creatorcontrib>Ihunnah, Chibueze A</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Chai, Xiaojuan</creatorcontrib><creatorcontrib>Zeng, Su</creatorcontrib><creatorcontrib>Philips, Brian J</creatorcontrib><creatorcontrib>Rubin, J. Peter</creatorcontrib><creatorcontrib>Marra, Kacey G</creatorcontrib><creatorcontrib>Xie, Wen</creatorcontrib><title>Estrogen Sulfotransferase Inhibits Adipocyte Differentiation</title><title>Molecular endocrinology (Baltimore, Md.)</title><addtitle>Mol Endocrinol</addtitle><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.</description><subject>3T3-L1 Cells</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - enzymology</subject><subject>Adipogenesis - drug effects</subject><subject>Adipogenesis - genetics</subject><subject>Adipose Tissue - drug effects</subject><subject>Adipose Tissue - enzymology</subject><subject>Animals</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Size - drug effects</subject><subject>Enzyme Activation - drug effects</subject><subject>Estradiol - pharmacology</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Insulin - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Original Research</subject><subject>PPAR gamma - agonists</subject><subject>PPAR gamma - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Sulfotransferases - genetics</subject><subject>Sulfotransferases - metabolism</subject><issn>0888-8809</issn><issn>1944-9917</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LAzEQQIMotn7cPMvevLg1s58JiFBq1ULBg3oOaXbSprTJkmyF_nu3bC0Kesph3rwMj5AroANIgN6tcZBQgBgo40ekDzzLYs6hPCZ9yhiLGaO8R85CWFIKWc7glPQSYFBwSvvkfhwa7-Zoo7fNSrvGSxs0ehkwmtiFmZkmRMPK1E5tG4wejW6HaBsjG-PsBTnRchXwcv-ek4-n8fvoJZ6-Pk9Gw2ms8iRvYkRZZmUps4SrilNI5axEkAqw4JWWqHSZJRoZYlrSLC0LzWSaKS4rJfMiz9Nz8tB5681sjZVqD_ByJWpv1tJvhZNG_J5YsxBz9ylSKHIOrBXcdgLlXQge9WEXqNhVFGsUu4piV7HFr3_-d4C_s7XATQe4Tf2fKt6r0o5EWznljcXaYwhi6Tbets3-PuALmHCNSw</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Wada, Taira</creator><creator>Ihunnah, Chibueze A</creator><creator>Gao, Jie</creator><creator>Chai, Xiaojuan</creator><creator>Zeng, Su</creator><creator>Philips, Brian J</creator><creator>Rubin, J. Peter</creator><creator>Marra, Kacey G</creator><creator>Xie, Wen</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20110901</creationdate><title>Estrogen Sulfotransferase Inhibits Adipocyte Differentiation</title><author>Wada, Taira ; Ihunnah, Chibueze A ; Gao, Jie ; Chai, Xiaojuan ; Zeng, Su ; Philips, Brian J ; Rubin, J. Peter ; Marra, Kacey G ; Xie, Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-eea7477a429cd9013ab7e1ac1e69dfaecf742fe8ee3704376f8a34c9adca56553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - enzymology</topic><topic>Adipogenesis - drug effects</topic><topic>Adipogenesis - genetics</topic><topic>Adipose Tissue - drug effects</topic><topic>Adipose Tissue - enzymology</topic><topic>Animals</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Size - drug effects</topic><topic>Enzyme Activation - drug effects</topic><topic>Estradiol - pharmacology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Gene Deletion</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Insulin - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Original Research</topic><topic>PPAR gamma - agonists</topic><topic>PPAR gamma - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Sulfotransferases - genetics</topic><topic>Sulfotransferases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wada, Taira</creatorcontrib><creatorcontrib>Ihunnah, Chibueze A</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Chai, Xiaojuan</creatorcontrib><creatorcontrib>Zeng, Su</creatorcontrib><creatorcontrib>Philips, Brian J</creatorcontrib><creatorcontrib>Rubin, J. Peter</creatorcontrib><creatorcontrib>Marra, Kacey G</creatorcontrib><creatorcontrib>Xie, Wen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wada, Taira</au><au>Ihunnah, Chibueze A</au><au>Gao, Jie</au><au>Chai, Xiaojuan</au><au>Zeng, Su</au><au>Philips, Brian J</au><au>Rubin, J. Peter</au><au>Marra, Kacey G</au><au>Xie, Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen Sulfotransferase Inhibits Adipocyte Differentiation</atitle><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle><addtitle>Mol Endocrinol</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>25</volume><issue>9</issue><spage>1612</spage><epage>1623</epage><pages>1612-1623</pages><issn>0888-8809</issn><eissn>1944-9917</eissn><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.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>21816900</pmid><doi>10.1210/me.2011-1089</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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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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