Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats
Objective The effects of the proliferator‐activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)‐β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed. Methods Six‐week‐old, male ZDF rats were fed a chow diet with (ZDF RO...
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| Veröffentlicht in: | Obesity (Silver Spring, Md.) Md.), 2014-07, Vol.22 (7), p.1632-1642 |
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| container_title | Obesity (Silver Spring, Md.) |
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| creator | Beaudoin, Marie‐Soleil Snook, Laelie A. Arkell, Alicia M. Stefanson, Amanda Wan, Zhongxiao Simpson, Jeremy A. Holloway, Graham P. Wright, David C. |
| description | Objective
The effects of the proliferator‐activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)‐β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed.
Methods
Six‐week‐old, male ZDF rats were fed a chow diet with (ZDF ROSI) or without (ZDF chow) ROSI (diet, 100 mg/kg) for 6 weeks. Subcutaneous (scWAT) and retroperitoneal (rpWAT) adipose tissues were excised to quantify the protein content/phosphorylation.
Results
ZDF ROSI animals showed enhanced glucose tolerance and mitochondrial protein content in both depots. The protein content of enzymes involved in fatty acid handling was increased in scWAT of ZDF ROSI animals. ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2. In contrast, ROSI increased the protein content of SMAD4, TGF‐β receptor I and II, and SMAD Anchor for Receptor Activation in scWAT.
Conclusions
For the first time, the fact that ROSI inhibits SMAD2 and SMAD3 signaling in a depot‐specific manner in diabetic rats was demonstrated. In scWAT, ROSI reduced SMAD2 and SMAD3 phosphorylation, likely through the inhibitory actions of SMAD7 and SMURF2. Induction of proximal components of the SMAD pathway may constitute a feedback mechanism to counteract ROSI‐induced lipid synthesis in scWAT. |
| doi_str_mv | 10.1002/oby.20717 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1542006286</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1542006286</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4587-ca70a5e8b6997574b27b1e9bcc5c31e39ad97fcfb73e6dc70ba7e9652b8dab253</originalsourceid><addsrcrecordid>eNp1kE1LxDAQQIMorq4e_AMS8KKHrknaNM3Rb4XVPaigp5KkU410m7VplfXXm92uHgRPMzCPB_MQ2qNkRAlhx07PR4wIKtbQFpUxiUQsn9Z_94wO0Lb3b4QkKeF0Ew1YwgkRIt1CxZ37gApDWYJpPXYlbpy3L5Vt1ZerAbsa39-enDOs6mK5xTica1XZ-gXbGn--2hawKuzMecCt9b6DhaWwSkNrDW5U63fQRqkqD7urOUSPlxcPZ9fReHJ1c3YyjkzCMxEZJYjikOlUSsFFopnQFKQ2hpuYQixVIUVpSi1iSAsjiFYCZMqZzgqlGY-H6LD3zhr33oFv86n1BqpK1eA6n1OeMEJSlqUBPfiDvrmuCX8FKhWcytAuDtRRT5lQxTdQ5rPGTlUzzynJF-nzkD5fpg_s_srY6SkUv-RP6wAc98CnrWD-vymfnD73ym9P4ozK</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1675191933</pqid></control><display><type>article</type><title>Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Beaudoin, Marie‐Soleil ; Snook, Laelie A. ; Arkell, Alicia M. ; Stefanson, Amanda ; Wan, Zhongxiao ; Simpson, Jeremy A. ; Holloway, Graham P. ; Wright, David C.</creator><creatorcontrib>Beaudoin, Marie‐Soleil ; Snook, Laelie A. ; Arkell, Alicia M. ; Stefanson, Amanda ; Wan, Zhongxiao ; Simpson, Jeremy A. ; Holloway, Graham P. ; Wright, David C.</creatorcontrib><description>Objective
The effects of the proliferator‐activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)‐β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed.
Methods
Six‐week‐old, male ZDF rats were fed a chow diet with (ZDF ROSI) or without (ZDF chow) ROSI (diet, 100 mg/kg) for 6 weeks. Subcutaneous (scWAT) and retroperitoneal (rpWAT) adipose tissues were excised to quantify the protein content/phosphorylation.
Results
ZDF ROSI animals showed enhanced glucose tolerance and mitochondrial protein content in both depots. The protein content of enzymes involved in fatty acid handling was increased in scWAT of ZDF ROSI animals. ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2. In contrast, ROSI increased the protein content of SMAD4, TGF‐β receptor I and II, and SMAD Anchor for Receptor Activation in scWAT.
Conclusions
For the first time, the fact that ROSI inhibits SMAD2 and SMAD3 signaling in a depot‐specific manner in diabetic rats was demonstrated. In scWAT, ROSI reduced SMAD2 and SMAD3 phosphorylation, likely through the inhibitory actions of SMAD7 and SMURF2. Induction of proximal components of the SMAD pathway may constitute a feedback mechanism to counteract ROSI‐induced lipid synthesis in scWAT.</description><identifier>ISSN: 1930-7381</identifier><identifier>EISSN: 1930-739X</identifier><identifier>DOI: 10.1002/oby.20717</identifier><identifier>PMID: 24500776</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adipose Tissue, White - drug effects ; Adipose Tissue, White - metabolism ; Animals ; Body fat ; Diabetes Mellitus, Experimental - metabolism ; Insulin ; Insulin resistance ; Kinases ; Laboratories ; Male ; PPAR gamma - agonists ; Protein-Serine-Threonine Kinases - metabolism ; Rats ; Rats, Zucker ; Receptors, Transforming Growth Factor beta - metabolism ; Rodents ; Signal Transduction - physiology ; Smad2 Protein - drug effects ; Smad2 Protein - metabolism ; Smad3 Protein - drug effects ; Smad3 Protein - metabolism ; Thiazolidinediones - pharmacology ; Transforming Growth Factor beta - metabolism</subject><ispartof>Obesity (Silver Spring, Md.), 2014-07, Vol.22 (7), p.1632-1642</ispartof><rights>Copyright © 2014 The Obesity Society</rights><rights>Copyright © 2014 The Obesity Society.</rights><rights>Copyright Blackwell Publishing Ltd. Jul 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4587-ca70a5e8b6997574b27b1e9bcc5c31e39ad97fcfb73e6dc70ba7e9652b8dab253</citedby><cites>FETCH-LOGICAL-c4587-ca70a5e8b6997574b27b1e9bcc5c31e39ad97fcfb73e6dc70ba7e9652b8dab253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Foby.20717$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Foby.20717$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24500776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beaudoin, Marie‐Soleil</creatorcontrib><creatorcontrib>Snook, Laelie A.</creatorcontrib><creatorcontrib>Arkell, Alicia M.</creatorcontrib><creatorcontrib>Stefanson, Amanda</creatorcontrib><creatorcontrib>Wan, Zhongxiao</creatorcontrib><creatorcontrib>Simpson, Jeremy A.</creatorcontrib><creatorcontrib>Holloway, Graham P.</creatorcontrib><creatorcontrib>Wright, David C.</creatorcontrib><title>Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats</title><title>Obesity (Silver Spring, Md.)</title><addtitle>Obesity (Silver Spring)</addtitle><description>Objective
The effects of the proliferator‐activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)‐β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed.
Methods
Six‐week‐old, male ZDF rats were fed a chow diet with (ZDF ROSI) or without (ZDF chow) ROSI (diet, 100 mg/kg) for 6 weeks. Subcutaneous (scWAT) and retroperitoneal (rpWAT) adipose tissues were excised to quantify the protein content/phosphorylation.
Results
ZDF ROSI animals showed enhanced glucose tolerance and mitochondrial protein content in both depots. The protein content of enzymes involved in fatty acid handling was increased in scWAT of ZDF ROSI animals. ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2. In contrast, ROSI increased the protein content of SMAD4, TGF‐β receptor I and II, and SMAD Anchor for Receptor Activation in scWAT.
Conclusions
For the first time, the fact that ROSI inhibits SMAD2 and SMAD3 signaling in a depot‐specific manner in diabetic rats was demonstrated. In scWAT, ROSI reduced SMAD2 and SMAD3 phosphorylation, likely through the inhibitory actions of SMAD7 and SMURF2. Induction of proximal components of the SMAD pathway may constitute a feedback mechanism to counteract ROSI‐induced lipid synthesis in scWAT.</description><subject>Adipose Tissue, White - drug effects</subject><subject>Adipose Tissue, White - metabolism</subject><subject>Animals</subject><subject>Body fat</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Male</subject><subject>PPAR gamma - agonists</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Rats</subject><subject>Rats, Zucker</subject><subject>Receptors, Transforming Growth Factor beta - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction - physiology</subject><subject>Smad2 Protein - drug effects</subject><subject>Smad2 Protein - metabolism</subject><subject>Smad3 Protein - drug effects</subject><subject>Smad3 Protein - metabolism</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>1930-7381</issn><issn>1930-739X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LxDAQQIMorq4e_AMS8KKHrknaNM3Rb4XVPaigp5KkU410m7VplfXXm92uHgRPMzCPB_MQ2qNkRAlhx07PR4wIKtbQFpUxiUQsn9Z_94wO0Lb3b4QkKeF0Ew1YwgkRIt1CxZ37gApDWYJpPXYlbpy3L5Vt1ZerAbsa39-enDOs6mK5xTica1XZ-gXbGn--2hawKuzMecCt9b6DhaWwSkNrDW5U63fQRqkqD7urOUSPlxcPZ9fReHJ1c3YyjkzCMxEZJYjikOlUSsFFopnQFKQ2hpuYQixVIUVpSi1iSAsjiFYCZMqZzgqlGY-H6LD3zhr33oFv86n1BqpK1eA6n1OeMEJSlqUBPfiDvrmuCX8FKhWcytAuDtRRT5lQxTdQ5rPGTlUzzynJF-nzkD5fpg_s_srY6SkUv-RP6wAc98CnrWD-vymfnD73ym9P4ozK</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Beaudoin, Marie‐Soleil</creator><creator>Snook, Laelie A.</creator><creator>Arkell, Alicia M.</creator><creator>Stefanson, Amanda</creator><creator>Wan, Zhongxiao</creator><creator>Simpson, Jeremy A.</creator><creator>Holloway, Graham P.</creator><creator>Wright, David C.</creator><general>Blackwell Publishing Ltd</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201407</creationdate><title>Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats</title><author>Beaudoin, Marie‐Soleil ; Snook, Laelie A. ; Arkell, Alicia M. ; Stefanson, Amanda ; Wan, Zhongxiao ; Simpson, Jeremy A. ; Holloway, Graham P. ; Wright, David C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4587-ca70a5e8b6997574b27b1e9bcc5c31e39ad97fcfb73e6dc70ba7e9652b8dab253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adipose Tissue, White - drug effects</topic><topic>Adipose Tissue, White - metabolism</topic><topic>Animals</topic><topic>Body fat</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Male</topic><topic>PPAR gamma - agonists</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Rats</topic><topic>Rats, Zucker</topic><topic>Receptors, Transforming Growth Factor beta - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction - physiology</topic><topic>Smad2 Protein - drug effects</topic><topic>Smad2 Protein - metabolism</topic><topic>Smad3 Protein - drug effects</topic><topic>Smad3 Protein - metabolism</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beaudoin, Marie‐Soleil</creatorcontrib><creatorcontrib>Snook, Laelie A.</creatorcontrib><creatorcontrib>Arkell, Alicia M.</creatorcontrib><creatorcontrib>Stefanson, Amanda</creatorcontrib><creatorcontrib>Wan, Zhongxiao</creatorcontrib><creatorcontrib>Simpson, Jeremy A.</creatorcontrib><creatorcontrib>Holloway, Graham P.</creatorcontrib><creatorcontrib>Wright, David C.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Obesity (Silver Spring, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beaudoin, Marie‐Soleil</au><au>Snook, Laelie A.</au><au>Arkell, Alicia M.</au><au>Stefanson, Amanda</au><au>Wan, Zhongxiao</au><au>Simpson, Jeremy A.</au><au>Holloway, Graham P.</au><au>Wright, David C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats</atitle><jtitle>Obesity (Silver Spring, Md.)</jtitle><addtitle>Obesity (Silver Spring)</addtitle><date>2014-07</date><risdate>2014</risdate><volume>22</volume><issue>7</issue><spage>1632</spage><epage>1642</epage><pages>1632-1642</pages><issn>1930-7381</issn><eissn>1930-739X</eissn><abstract>Objective
The effects of the proliferator‐activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)‐β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed.
Methods
Six‐week‐old, male ZDF rats were fed a chow diet with (ZDF ROSI) or without (ZDF chow) ROSI (diet, 100 mg/kg) for 6 weeks. Subcutaneous (scWAT) and retroperitoneal (rpWAT) adipose tissues were excised to quantify the protein content/phosphorylation.
Results
ZDF ROSI animals showed enhanced glucose tolerance and mitochondrial protein content in both depots. The protein content of enzymes involved in fatty acid handling was increased in scWAT of ZDF ROSI animals. ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2. In contrast, ROSI increased the protein content of SMAD4, TGF‐β receptor I and II, and SMAD Anchor for Receptor Activation in scWAT.
Conclusions
For the first time, the fact that ROSI inhibits SMAD2 and SMAD3 signaling in a depot‐specific manner in diabetic rats was demonstrated. In scWAT, ROSI reduced SMAD2 and SMAD3 phosphorylation, likely through the inhibitory actions of SMAD7 and SMURF2. Induction of proximal components of the SMAD pathway may constitute a feedback mechanism to counteract ROSI‐induced lipid synthesis in scWAT.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24500776</pmid><doi>10.1002/oby.20717</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Obesity (Silver Spring, Md.), 2014-07, Vol.22 (7), p.1632-1642 |
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| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adipose Tissue, White - drug effects Adipose Tissue, White - metabolism Animals Body fat Diabetes Mellitus, Experimental - metabolism Insulin Insulin resistance Kinases Laboratories Male PPAR gamma - agonists Protein-Serine-Threonine Kinases - metabolism Rats Rats, Zucker Receptors, Transforming Growth Factor beta - metabolism Rodents Signal Transduction - physiology Smad2 Protein - drug effects Smad2 Protein - metabolism Smad3 Protein - drug effects Smad3 Protein - metabolism Thiazolidinediones - pharmacology Transforming Growth Factor beta - metabolism |
| title | Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats |
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