Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction

NYGGF4 , also known as phosphotyrosine interaction domain containing 1( PID1 ), is a recently discovered gene which is involved in obesity-related insulin resistance (IR) and mitochondrial dysfunction. We aimed to further elucidate the effects and mechanisms underlying NYGGF4-induced IR by investiga...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cell biochemistry and biophysics 2013-07, Vol.66 (3), p.489-497
Hauptverfasser: Shi, Chun-Mei, Xu, Guang-Feng, Yang, Lei, Fu, Zi-Yi, Chen, Ling, Fu, Hai-Long, Shen, Ya-Hui, Zhu, Lu, Ji, Chen-Bo, Guo, Xi-Rong
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 497
container_issue 3
container_start_page 489
container_title Cell biochemistry and biophysics
container_volume 66
creator Shi, Chun-Mei
Xu, Guang-Feng
Yang, Lei
Fu, Zi-Yi
Chen, Ling
Fu, Hai-Long
Shen, Ya-Hui
Zhu, Lu
Ji, Chen-Bo
Guo, Xi-Rong
description NYGGF4 , also known as phosphotyrosine interaction domain containing 1( PID1 ), is a recently discovered gene which is involved in obesity-related insulin resistance (IR) and mitochondrial dysfunction. We aimed to further elucidate the effects and mechanisms underlying NYGGF4-induced IR by investigating the effect of overexpressing mitochondrial transcription factor A (TFAM), which is essential for mitochondrial DNA transcription and replication, on NYGGF4-induced IR and mitochondrial abnormalities in 3T3-L1 adipocytes. Overexpression of TFAM increased the mitochondrial copy number and ATP content in both control 3T3-L1 adipocytes and NYGGF4-overexpressing adipocytes. Reactive oxygen species (ROS) production was enhanced in NYGGF4-overexpressing adipocytes and reduced in TFAM-overexpressing adipocytes; co-overexpression of TFAM significantly attenuated ROS production in NYGGF4-overexpressing adipocytes. However, overexpression of TFAM did not affect the mitochondrial transmembrane potential (ΔΨm) in control 3T3-L1 adipocytes or NYGGF4-overexpressing adipocytes. In addition, co-overexpression of TFAM-enhanced insulin-stimulated glucose uptake by increasing Glucose transporter type 4 (GLUT4) translocation to the PM in NYGGF4-overexpressing adipocytes. Overexpression of NYGGF4 significantly inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. This study demonstrates that NYGGF4 plays a role in IR by impairing mitochondrial function, and that overexpression of TFAM can restore mitochondrial function to normal levels in NYGGF4-overexpressing adipocytes via activation of the IRS-1/PI3K/Akt signaling pathway.
doi_str_mv 10.1007/s12013-012-9496-1
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1416044265</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3031310631</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-3ca40986e2356c8266a56fa3b57f78e5132ebdda8f51acb200056db1411fe8aa3</originalsourceid><addsrcrecordid>eNp1kctuEzEUhi1ERS_wAGyQJTbtwsXHHs9lGbUkREpphcKCleWxz8BUEzvYM4i8Aw-No5SKIrGyJX__76PzEfIa-CVwXr1LIDhIxkGwpmhKBs_ICSjVMC5q-Tzfea1YA406Jqcp3XMuBC-KF-RYSFEVDcgT8uv2B0b8uY2YUh88DR1dz2c39C6GEe2YqFxLtgI6c_022N2IiXYxbOjHL4vFvKDnd8truKBPS9jSu8mio0ufpqH39BOmPo3GW6TGO3rTj8F-C97F3gz0epe6ydsxB1-So84MCV89nGfk8_z9-uoDW90ullezFbOyEiOT1hS8qUsUUpW2FmVpVNkZ2aqqq2pUIAW2zpm6U2BsKzjnqnQtFAAd1sbIM3J-6N3G8H3CNOpNnywOg_EYpqQzWeZFiVJl9O0_6H2Yos_T7Sm5n6MuMgUHysaQUsROb2O_MXGngeu9Kn1QpbMqvVelIWfePDRP7QbdY-KPmwyIA5Dyk_-K8a-v_9v6G0vKnes</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1413409884</pqid></control><display><type>article</type><title>Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Shi, Chun-Mei ; Xu, Guang-Feng ; Yang, Lei ; Fu, Zi-Yi ; Chen, Ling ; Fu, Hai-Long ; Shen, Ya-Hui ; Zhu, Lu ; Ji, Chen-Bo ; Guo, Xi-Rong</creator><creatorcontrib>Shi, Chun-Mei ; Xu, Guang-Feng ; Yang, Lei ; Fu, Zi-Yi ; Chen, Ling ; Fu, Hai-Long ; Shen, Ya-Hui ; Zhu, Lu ; Ji, Chen-Bo ; Guo, Xi-Rong</creatorcontrib><description>NYGGF4 , also known as phosphotyrosine interaction domain containing 1( PID1 ), is a recently discovered gene which is involved in obesity-related insulin resistance (IR) and mitochondrial dysfunction. We aimed to further elucidate the effects and mechanisms underlying NYGGF4-induced IR by investigating the effect of overexpressing mitochondrial transcription factor A (TFAM), which is essential for mitochondrial DNA transcription and replication, on NYGGF4-induced IR and mitochondrial abnormalities in 3T3-L1 adipocytes. Overexpression of TFAM increased the mitochondrial copy number and ATP content in both control 3T3-L1 adipocytes and NYGGF4-overexpressing adipocytes. Reactive oxygen species (ROS) production was enhanced in NYGGF4-overexpressing adipocytes and reduced in TFAM-overexpressing adipocytes; co-overexpression of TFAM significantly attenuated ROS production in NYGGF4-overexpressing adipocytes. However, overexpression of TFAM did not affect the mitochondrial transmembrane potential (ΔΨm) in control 3T3-L1 adipocytes or NYGGF4-overexpressing adipocytes. In addition, co-overexpression of TFAM-enhanced insulin-stimulated glucose uptake by increasing Glucose transporter type 4 (GLUT4) translocation to the PM in NYGGF4-overexpressing adipocytes. Overexpression of NYGGF4 significantly inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. This study demonstrates that NYGGF4 plays a role in IR by impairing mitochondrial function, and that overexpression of TFAM can restore mitochondrial function to normal levels in NYGGF4-overexpressing adipocytes via activation of the IRS-1/PI3K/Akt signaling pathway.</description><identifier>ISSN: 1085-9195</identifier><identifier>EISSN: 1559-0283</identifier><identifier>DOI: 10.1007/s12013-012-9496-1</identifier><identifier>PMID: 23274913</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>3T3-L1 Cells ; Adenosine Triphosphate - metabolism ; Adipocytes - drug effects ; Adipocytes - metabolism ; Adipocytes - pathology ; Animals ; Biochemistry ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biophysics ; Biotechnology ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Biology ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Gene Expression ; Glucose - metabolism ; Glucose Transporter Type 4 - metabolism ; Insulin - metabolism ; Insulin - pharmacology ; Insulin Resistance ; Life Sciences ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondria - pathology ; Mitochondrial DNA ; Mitochondrial Proteins - genetics ; Mitochondrial Proteins - metabolism ; Mitochondrial Size - drug effects ; Original Paper ; Pharmacology/Toxicology ; Phosphorylation - drug effects ; Protein Transport - drug effects ; Reactive Oxygen Species - metabolism ; Signal Transduction - drug effects ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Translocation</subject><ispartof>Cell biochemistry and biophysics, 2013-07, Vol.66 (3), p.489-497</ispartof><rights>Springer Science+Business Media New York 2012</rights><rights>Springer Science+Business Media New York 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-3ca40986e2356c8266a56fa3b57f78e5132ebdda8f51acb200056db1411fe8aa3</citedby><cites>FETCH-LOGICAL-c372t-3ca40986e2356c8266a56fa3b57f78e5132ebdda8f51acb200056db1411fe8aa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12013-012-9496-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12013-012-9496-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23274913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shi, Chun-Mei</creatorcontrib><creatorcontrib>Xu, Guang-Feng</creatorcontrib><creatorcontrib>Yang, Lei</creatorcontrib><creatorcontrib>Fu, Zi-Yi</creatorcontrib><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Fu, Hai-Long</creatorcontrib><creatorcontrib>Shen, Ya-Hui</creatorcontrib><creatorcontrib>Zhu, Lu</creatorcontrib><creatorcontrib>Ji, Chen-Bo</creatorcontrib><creatorcontrib>Guo, Xi-Rong</creatorcontrib><title>Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction</title><title>Cell biochemistry and biophysics</title><addtitle>Cell Biochem Biophys</addtitle><addtitle>Cell Biochem Biophys</addtitle><description>NYGGF4 , also known as phosphotyrosine interaction domain containing 1( PID1 ), is a recently discovered gene which is involved in obesity-related insulin resistance (IR) and mitochondrial dysfunction. We aimed to further elucidate the effects and mechanisms underlying NYGGF4-induced IR by investigating the effect of overexpressing mitochondrial transcription factor A (TFAM), which is essential for mitochondrial DNA transcription and replication, on NYGGF4-induced IR and mitochondrial abnormalities in 3T3-L1 adipocytes. Overexpression of TFAM increased the mitochondrial copy number and ATP content in both control 3T3-L1 adipocytes and NYGGF4-overexpressing adipocytes. Reactive oxygen species (ROS) production was enhanced in NYGGF4-overexpressing adipocytes and reduced in TFAM-overexpressing adipocytes; co-overexpression of TFAM significantly attenuated ROS production in NYGGF4-overexpressing adipocytes. However, overexpression of TFAM did not affect the mitochondrial transmembrane potential (ΔΨm) in control 3T3-L1 adipocytes or NYGGF4-overexpressing adipocytes. In addition, co-overexpression of TFAM-enhanced insulin-stimulated glucose uptake by increasing Glucose transporter type 4 (GLUT4) translocation to the PM in NYGGF4-overexpressing adipocytes. Overexpression of NYGGF4 significantly inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. This study demonstrates that NYGGF4 plays a role in IR by impairing mitochondrial function, and that overexpression of TFAM can restore mitochondrial function to normal levels in NYGGF4-overexpressing adipocytes via activation of the IRS-1/PI3K/Akt signaling pathway.</description><subject>3T3-L1 Cells</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Adipocytes - pathology</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Biotechnology</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Biology</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression</subject><subject>Glucose - metabolism</subject><subject>Glucose Transporter Type 4 - metabolism</subject><subject>Insulin - metabolism</subject><subject>Insulin - pharmacology</subject><subject>Insulin Resistance</subject><subject>Life Sciences</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial DNA</subject><subject>Mitochondrial Proteins - genetics</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Mitochondrial Size - drug effects</subject><subject>Original Paper</subject><subject>Pharmacology/Toxicology</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Transport - drug effects</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Translocation</subject><issn>1085-9195</issn><issn>1559-0283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kctuEzEUhi1ERS_wAGyQJTbtwsXHHs9lGbUkREpphcKCleWxz8BUEzvYM4i8Aw-No5SKIrGyJX__76PzEfIa-CVwXr1LIDhIxkGwpmhKBs_ICSjVMC5q-Tzfea1YA406Jqcp3XMuBC-KF-RYSFEVDcgT8uv2B0b8uY2YUh88DR1dz2c39C6GEe2YqFxLtgI6c_022N2IiXYxbOjHL4vFvKDnd8truKBPS9jSu8mio0ufpqH39BOmPo3GW6TGO3rTj8F-C97F3gz0epe6ydsxB1-So84MCV89nGfk8_z9-uoDW90ullezFbOyEiOT1hS8qUsUUpW2FmVpVNkZ2aqqq2pUIAW2zpm6U2BsKzjnqnQtFAAd1sbIM3J-6N3G8H3CNOpNnywOg_EYpqQzWeZFiVJl9O0_6H2Yos_T7Sm5n6MuMgUHysaQUsROb2O_MXGngeu9Kn1QpbMqvVelIWfePDRP7QbdY-KPmwyIA5Dyk_-K8a-v_9v6G0vKnes</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Shi, Chun-Mei</creator><creator>Xu, Guang-Feng</creator><creator>Yang, Lei</creator><creator>Fu, Zi-Yi</creator><creator>Chen, Ling</creator><creator>Fu, Hai-Long</creator><creator>Shen, Ya-Hui</creator><creator>Zhu, Lu</creator><creator>Ji, Chen-Bo</creator><creator>Guo, Xi-Rong</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20130701</creationdate><title>Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction</title><author>Shi, Chun-Mei ; Xu, Guang-Feng ; Yang, Lei ; Fu, Zi-Yi ; Chen, Ling ; Fu, Hai-Long ; Shen, Ya-Hui ; Zhu, Lu ; Ji, Chen-Bo ; Guo, Xi-Rong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-3ca40986e2356c8266a56fa3b57f78e5132ebdda8f51acb200056db1411fe8aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3T3-L1 Cells</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Adipocytes - pathology</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and Medical Physics</topic><topic>Biomedical and Life Sciences</topic><topic>Biophysics</topic><topic>Biotechnology</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Biology</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression</topic><topic>Glucose - metabolism</topic><topic>Glucose Transporter Type 4 - metabolism</topic><topic>Insulin - metabolism</topic><topic>Insulin - pharmacology</topic><topic>Insulin Resistance</topic><topic>Life Sciences</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial DNA</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Mitochondrial Size - drug effects</topic><topic>Original Paper</topic><topic>Pharmacology/Toxicology</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Transport - drug effects</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shi, Chun-Mei</creatorcontrib><creatorcontrib>Xu, Guang-Feng</creatorcontrib><creatorcontrib>Yang, Lei</creatorcontrib><creatorcontrib>Fu, Zi-Yi</creatorcontrib><creatorcontrib>Chen, Ling</creatorcontrib><creatorcontrib>Fu, Hai-Long</creatorcontrib><creatorcontrib>Shen, Ya-Hui</creatorcontrib><creatorcontrib>Zhu, Lu</creatorcontrib><creatorcontrib>Ji, Chen-Bo</creatorcontrib><creatorcontrib>Guo, Xi-Rong</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 Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shi, Chun-Mei</au><au>Xu, Guang-Feng</au><au>Yang, Lei</au><au>Fu, Zi-Yi</au><au>Chen, Ling</au><au>Fu, Hai-Long</au><au>Shen, Ya-Hui</au><au>Zhu, Lu</au><au>Ji, Chen-Bo</au><au>Guo, Xi-Rong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction</atitle><jtitle>Cell biochemistry and biophysics</jtitle><stitle>Cell Biochem Biophys</stitle><addtitle>Cell Biochem Biophys</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>66</volume><issue>3</issue><spage>489</spage><epage>497</epage><pages>489-497</pages><issn>1085-9195</issn><eissn>1559-0283</eissn><abstract>NYGGF4 , also known as phosphotyrosine interaction domain containing 1( PID1 ), is a recently discovered gene which is involved in obesity-related insulin resistance (IR) and mitochondrial dysfunction. We aimed to further elucidate the effects and mechanisms underlying NYGGF4-induced IR by investigating the effect of overexpressing mitochondrial transcription factor A (TFAM), which is essential for mitochondrial DNA transcription and replication, on NYGGF4-induced IR and mitochondrial abnormalities in 3T3-L1 adipocytes. Overexpression of TFAM increased the mitochondrial copy number and ATP content in both control 3T3-L1 adipocytes and NYGGF4-overexpressing adipocytes. Reactive oxygen species (ROS) production was enhanced in NYGGF4-overexpressing adipocytes and reduced in TFAM-overexpressing adipocytes; co-overexpression of TFAM significantly attenuated ROS production in NYGGF4-overexpressing adipocytes. However, overexpression of TFAM did not affect the mitochondrial transmembrane potential (ΔΨm) in control 3T3-L1 adipocytes or NYGGF4-overexpressing adipocytes. In addition, co-overexpression of TFAM-enhanced insulin-stimulated glucose uptake by increasing Glucose transporter type 4 (GLUT4) translocation to the PM in NYGGF4-overexpressing adipocytes. Overexpression of NYGGF4 significantly inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. This study demonstrates that NYGGF4 plays a role in IR by impairing mitochondrial function, and that overexpression of TFAM can restore mitochondrial function to normal levels in NYGGF4-overexpressing adipocytes via activation of the IRS-1/PI3K/Akt signaling pathway.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23274913</pmid><doi>10.1007/s12013-012-9496-1</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 1085-9195
ispartof Cell biochemistry and biophysics, 2013-07, Vol.66 (3), p.489-497
issn 1085-9195
1559-0283
language eng
recordid cdi_proquest_miscellaneous_1416044265
source MEDLINE; SpringerLink Journals - AutoHoldings
subjects 3T3-L1 Cells
Adenosine Triphosphate - metabolism
Adipocytes - drug effects
Adipocytes - metabolism
Adipocytes - pathology
Animals
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biophysics
Biotechnology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Biology
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene Expression
Glucose - metabolism
Glucose Transporter Type 4 - metabolism
Insulin - metabolism
Insulin - pharmacology
Insulin Resistance
Life Sciences
Membrane Potential, Mitochondrial - drug effects
Mice
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria - pathology
Mitochondrial DNA
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Mitochondrial Size - drug effects
Original Paper
Pharmacology/Toxicology
Phosphorylation - drug effects
Protein Transport - drug effects
Reactive Oxygen Species - metabolism
Signal Transduction - drug effects
Transcription Factors - genetics
Transcription Factors - metabolism
Translocation
title Overexpression of TFAM Protects 3T3-L1 Adipocytes from NYGGF4 (PID1) Overexpression-Induced Insulin Resistance and Mitochondrial Dysfunction
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T17%3A26%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Overexpression%20of%20TFAM%20Protects%203T3-L1%20Adipocytes%20from%20NYGGF4%20(PID1)%20Overexpression-Induced%20Insulin%20Resistance%20and%20Mitochondrial%20Dysfunction&rft.jtitle=Cell%20biochemistry%20and%20biophysics&rft.au=Shi,%20Chun-Mei&rft.date=2013-07-01&rft.volume=66&rft.issue=3&rft.spage=489&rft.epage=497&rft.pages=489-497&rft.issn=1085-9195&rft.eissn=1559-0283&rft_id=info:doi/10.1007/s12013-012-9496-1&rft_dat=%3Cproquest_cross%3E3031310631%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1413409884&rft_id=info:pmid/23274913&rfr_iscdi=true