Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone James X. Rong 1 , Yang Qiu 2 3 , Michael K. Hansen 3 , Lei Zhu 3 4 , Vivian Zhang 3 , Mi Xie 1 , Yuji Okamoto 5 , Michael D. Mattie 6 , Hiroyuki Higashiyama 5 , Satoshi Asano 5 , Jay C. S...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2007-07, Vol.56 (7), p.1751-1760 |
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| creator | RONG, James X YANG QIU STRUM, Jay C RYAN, Terence E HANSEN, Michael K LEI ZHU ZHANG, Vivian MI XIE OKAMOTO, Yuji MATTIE, Michael D HIGASHIYAMA, Hiroyuki ASANO, Satoshi |
| description | Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
James X. Rong 1 ,
Yang Qiu 2 3 ,
Michael K. Hansen 3 ,
Lei Zhu 3 4 ,
Vivian Zhang 3 ,
Mi Xie 1 ,
Yuji Okamoto 5 ,
Michael D. Mattie 6 ,
Hiroyuki Higashiyama 5 ,
Satoshi Asano 5 ,
Jay C. Strum 6 and
Terence E. Ryan 3
1 High Throughput Biology, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
2 Cheminformatics, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
3 Integrative Biology, High Throughput Biology, Discovery Research, GlaxoSmithKline, King of Prussia, Pennsylvania
4 Biomedical Data Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina
5 Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, Ibaraki, Japan
6 Department of Quantitative Expression, Genetics Research, GlaxoSmithKline, Research Triangle Park, North Carolina
Address correspondence and reprint requests to James X. Rong, High Throughput Biology, Discovery Research, GlaxoSmithKline,
5 Moore Dr., Research Triangle Park, NC. E-mail: james.x.rong{at}gsk.com
Abstract
The objective of this study was to further establish and confirm the relationship of adipose mitochondrial biogenesis in diabetes/obesity
and the effects of rosiglitazone (RSG), a peroxisome proliferator–activated receptor (PPAR) γ agonist, by systematically analyzing
mitochondrial gene expression and function in two mouse models of obesity and type 2 diabetes. Using microarray technology,
adipose mitochondrial gene transcription was studied in db/db , high-fat diet–fed C57BL/6 (HFD) and respective control mice with or without RSG treatment. The findings were extended using
mitochondrial staining, DNA quantification, and measurements of citrate synthase activity. In db/db and HFD mice, gene transcripts associated with mitochondrial ATP production, energy uncoupling, mitochondrial ribosomal proteins,
outer and inner membrane translocases, and mitochondrial heat-shock proteins were decreased in abundance, compared with db/+
and standard-fat diet–fed control mice, respectively. RSG dose-dependently increased these transcripts in both db/db and HFD mice and induced transcription of mitochondrial structural proteins and cellular antioxidant enzymes responsible
for removal of reactive oxygen species generated by increased mitochondrial activity. Transcription factors, including PPAR
coactivator (PGC)-1β, PGC-1α, estrogen-relat |
| doi_str_mv | 10.2337/db06-1135 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_216483961</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A166823605</galeid><sourcerecordid>A166823605</sourcerecordid><originalsourceid>FETCH-LOGICAL-c551t-b9ffe12248769de8c638a417c4bf57ab6a14690394b8560ed9d39f1778d082033</originalsourceid><addsrcrecordid>eNpt0t2K1DAUB_AiijuuXvgCUgQFka5J03xdjqOzOzDLgh_gXUiT006WTjMmrbpe-Q6-4T7JZpyBYWXIRUL6y0l6-GfZc4zOSkL4O1sjVmBM6INsgiWRBSn5t4fZBCFcFphLfpI9ifEaIcTSeJydYF5RJmg1ycLUuo2PkF-6wZuV721wusvfO99CD9HFfBHzz-NmEyBGsLnrc1unC3Pd2_zCtatirof8g4Ph9s_feQKXzsC_j4v1Jvgfaae-yT_56NrODfq37-Fp9qjRXYRn-_k0-zr_-GV2USyvzhez6bIwlOKhqGXTAC7LSnAmLQjDiNAV5qaqG8p1zTSumEREVrWgDIGVlsgGcy4sEiUi5DR7vaub3vF9hDiotYsGuk734MeoOGKMynILX_4Hr_0Y-vQ2VWJWCSIZTqjYoVZ3oFzf-CFos21S0F36q8al7SlmTJSEIZr82RGfhoW1M0cPvLl3IJkBfg2tHmNU4nx53xbHrPFdBy2o1MbZ1dHaJvgYAzRqE9xahxuFkdpGSG0jpLYRSvbFvhtjvQZ7kPvMJPBqD3Q0umuC7o2LBydkKTlhyb3duVWKyU8XQFmnaxggHhaUKZ4qU0zuAGV-2X4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>216483961</pqid></control><display><type>article</type><title>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone</title><source>MEDLINE</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>RONG, James X ; YANG QIU ; STRUM, Jay C ; RYAN, Terence E ; HANSEN, Michael K ; LEI ZHU ; ZHANG, Vivian ; MI XIE ; OKAMOTO, Yuji ; MATTIE, Michael D ; HIGASHIYAMA, Hiroyuki ; ASANO, Satoshi</creator><creatorcontrib>RONG, James X ; YANG QIU ; STRUM, Jay C ; RYAN, Terence E ; HANSEN, Michael K ; LEI ZHU ; ZHANG, Vivian ; MI XIE ; OKAMOTO, Yuji ; MATTIE, Michael D ; HIGASHIYAMA, Hiroyuki ; ASANO, Satoshi</creatorcontrib><description>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
James X. Rong 1 ,
Yang Qiu 2 3 ,
Michael K. Hansen 3 ,
Lei Zhu 3 4 ,
Vivian Zhang 3 ,
Mi Xie 1 ,
Yuji Okamoto 5 ,
Michael D. Mattie 6 ,
Hiroyuki Higashiyama 5 ,
Satoshi Asano 5 ,
Jay C. Strum 6 and
Terence E. Ryan 3
1 High Throughput Biology, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
2 Cheminformatics, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
3 Integrative Biology, High Throughput Biology, Discovery Research, GlaxoSmithKline, King of Prussia, Pennsylvania
4 Biomedical Data Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina
5 Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, Ibaraki, Japan
6 Department of Quantitative Expression, Genetics Research, GlaxoSmithKline, Research Triangle Park, North Carolina
Address correspondence and reprint requests to James X. Rong, High Throughput Biology, Discovery Research, GlaxoSmithKline,
5 Moore Dr., Research Triangle Park, NC. E-mail: james.x.rong{at}gsk.com
Abstract
The objective of this study was to further establish and confirm the relationship of adipose mitochondrial biogenesis in diabetes/obesity
and the effects of rosiglitazone (RSG), a peroxisome proliferator–activated receptor (PPAR) γ agonist, by systematically analyzing
mitochondrial gene expression and function in two mouse models of obesity and type 2 diabetes. Using microarray technology,
adipose mitochondrial gene transcription was studied in db/db , high-fat diet–fed C57BL/6 (HFD) and respective control mice with or without RSG treatment. The findings were extended using
mitochondrial staining, DNA quantification, and measurements of citrate synthase activity. In db/db and HFD mice, gene transcripts associated with mitochondrial ATP production, energy uncoupling, mitochondrial ribosomal proteins,
outer and inner membrane translocases, and mitochondrial heat-shock proteins were decreased in abundance, compared with db/+
and standard-fat diet–fed control mice, respectively. RSG dose-dependently increased these transcripts in both db/db and HFD mice and induced transcription of mitochondrial structural proteins and cellular antioxidant enzymes responsible
for removal of reactive oxygen species generated by increased mitochondrial activity. Transcription factors, including PPAR
coactivator (PGC)-1β, PGC-1α, estrogen-related receptor α, and PPARα, were suppressed in both models and induced by RSG. The
effects of RSG on adipose mitochondrial genes were confirmed by quantitative RT-PCR and further supported by mitochondrial
staining, mitochondrial DNA quantification, and citrate synthase activity. Adipose mitochondrial biogenesis was overwhelmingly
suppressed in both mouse models of diabetes/obesity and globally induced by RSG. These findings suggest an important role
of adipose mitochondria in diabetes/obesity and the potential for new treatment approaches targeting adipose mitochondria.
BAT, brown adipose tissue
CIDEA, cell death–inducing DFFA-like effector a
CPT, carnitinepalmitoyl transferase
FAO, fatty acid oxidation
HSP, heat-shock protein
OXPHOS, oxidative phosphorylation
PGC, PPAR coactivator
PPAR, peroxisome proliferator–activated receptor
RIP, receptor interacting protein
RSG, rosiglitazone
TCA, tricarboxylic acid
UCP, uncoupling protein
WAT, white adipose tissue
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 24 April 2007. DOI: 10.2337/db06-1135.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1135 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted April 11, 2007.
Received August 14, 2006.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db06-1135</identifier><identifier>PMID: 17456854</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adipose tissue ; Adipose Tissue - drug effects ; Adipose Tissue - metabolism ; Adipose tissues ; Animals ; Biological and medical sciences ; Biosynthesis ; Body fat ; Cytochrome ; Diabetes ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes. Impaired glucose tolerance ; Diet ; Dietary Fats ; Disease Models, Animal ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Gene Expression ; Gene Expression Profiling ; Genetic aspects ; Glucose ; Hypoglycemic Agents - pharmacology ; Insulin ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondrial DNA ; Obesity ; Obesity - drug therapy ; PPAR gamma - agonists ; Proteins ; Risk factors ; Thiazolidinediones - pharmacology ; Transcription factors ; Transcription, Genetic ; Type 2 diabetes</subject><ispartof>Diabetes (New York, N.Y.), 2007-07, Vol.56 (7), p.1751-1760</ispartof><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2007 American Diabetes Association</rights><rights>Copyright American Diabetes Association Jul 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c551t-b9ffe12248769de8c638a417c4bf57ab6a14690394b8560ed9d39f1778d082033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18929736$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17456854$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RONG, James X</creatorcontrib><creatorcontrib>YANG QIU</creatorcontrib><creatorcontrib>STRUM, Jay C</creatorcontrib><creatorcontrib>RYAN, Terence E</creatorcontrib><creatorcontrib>HANSEN, Michael K</creatorcontrib><creatorcontrib>LEI ZHU</creatorcontrib><creatorcontrib>ZHANG, Vivian</creatorcontrib><creatorcontrib>MI XIE</creatorcontrib><creatorcontrib>OKAMOTO, Yuji</creatorcontrib><creatorcontrib>MATTIE, Michael D</creatorcontrib><creatorcontrib>HIGASHIYAMA, Hiroyuki</creatorcontrib><creatorcontrib>ASANO, Satoshi</creatorcontrib><title>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
James X. Rong 1 ,
Yang Qiu 2 3 ,
Michael K. Hansen 3 ,
Lei Zhu 3 4 ,
Vivian Zhang 3 ,
Mi Xie 1 ,
Yuji Okamoto 5 ,
Michael D. Mattie 6 ,
Hiroyuki Higashiyama 5 ,
Satoshi Asano 5 ,
Jay C. Strum 6 and
Terence E. Ryan 3
1 High Throughput Biology, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
2 Cheminformatics, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
3 Integrative Biology, High Throughput Biology, Discovery Research, GlaxoSmithKline, King of Prussia, Pennsylvania
4 Biomedical Data Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina
5 Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, Ibaraki, Japan
6 Department of Quantitative Expression, Genetics Research, GlaxoSmithKline, Research Triangle Park, North Carolina
Address correspondence and reprint requests to James X. Rong, High Throughput Biology, Discovery Research, GlaxoSmithKline,
5 Moore Dr., Research Triangle Park, NC. E-mail: james.x.rong{at}gsk.com
Abstract
The objective of this study was to further establish and confirm the relationship of adipose mitochondrial biogenesis in diabetes/obesity
and the effects of rosiglitazone (RSG), a peroxisome proliferator–activated receptor (PPAR) γ agonist, by systematically analyzing
mitochondrial gene expression and function in two mouse models of obesity and type 2 diabetes. Using microarray technology,
adipose mitochondrial gene transcription was studied in db/db , high-fat diet–fed C57BL/6 (HFD) and respective control mice with or without RSG treatment. The findings were extended using
mitochondrial staining, DNA quantification, and measurements of citrate synthase activity. In db/db and HFD mice, gene transcripts associated with mitochondrial ATP production, energy uncoupling, mitochondrial ribosomal proteins,
outer and inner membrane translocases, and mitochondrial heat-shock proteins were decreased in abundance, compared with db/+
and standard-fat diet–fed control mice, respectively. RSG dose-dependently increased these transcripts in both db/db and HFD mice and induced transcription of mitochondrial structural proteins and cellular antioxidant enzymes responsible
for removal of reactive oxygen species generated by increased mitochondrial activity. Transcription factors, including PPAR
coactivator (PGC)-1β, PGC-1α, estrogen-related receptor α, and PPARα, were suppressed in both models and induced by RSG. The
effects of RSG on adipose mitochondrial genes were confirmed by quantitative RT-PCR and further supported by mitochondrial
staining, mitochondrial DNA quantification, and citrate synthase activity. Adipose mitochondrial biogenesis was overwhelmingly
suppressed in both mouse models of diabetes/obesity and globally induced by RSG. These findings suggest an important role
of adipose mitochondria in diabetes/obesity and the potential for new treatment approaches targeting adipose mitochondria.
BAT, brown adipose tissue
CIDEA, cell death–inducing DFFA-like effector a
CPT, carnitinepalmitoyl transferase
FAO, fatty acid oxidation
HSP, heat-shock protein
OXPHOS, oxidative phosphorylation
PGC, PPAR coactivator
PPAR, peroxisome proliferator–activated receptor
RIP, receptor interacting protein
RSG, rosiglitazone
TCA, tricarboxylic acid
UCP, uncoupling protein
WAT, white adipose tissue
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 24 April 2007. DOI: 10.2337/db06-1135.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1135 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted April 11, 2007.
Received August 14, 2006.
DIABETES</description><subject>Adipose tissue</subject><subject>Adipose Tissue - drug effects</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose tissues</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biosynthesis</subject><subject>Body fat</subject><subject>Cytochrome</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet</subject><subject>Dietary Fats</subject><subject>Disease Models, Animal</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Genetic aspects</subject><subject>Glucose</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondria</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondrial DNA</subject><subject>Obesity</subject><subject>Obesity - drug therapy</subject><subject>PPAR gamma - agonists</subject><subject>Proteins</subject><subject>Risk factors</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Transcription factors</subject><subject>Transcription, Genetic</subject><subject>Type 2 diabetes</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0t2K1DAUB_AiijuuXvgCUgQFka5J03xdjqOzOzDLgh_gXUiT006WTjMmrbpe-Q6-4T7JZpyBYWXIRUL6y0l6-GfZc4zOSkL4O1sjVmBM6INsgiWRBSn5t4fZBCFcFphLfpI9ifEaIcTSeJydYF5RJmg1ycLUuo2PkF-6wZuV721wusvfO99CD9HFfBHzz-NmEyBGsLnrc1unC3Pd2_zCtatirof8g4Ph9s_feQKXzsC_j4v1Jvgfaae-yT_56NrODfq37-Fp9qjRXYRn-_k0-zr_-GV2USyvzhez6bIwlOKhqGXTAC7LSnAmLQjDiNAV5qaqG8p1zTSumEREVrWgDIGVlsgGcy4sEiUi5DR7vaub3vF9hDiotYsGuk734MeoOGKMynILX_4Hr_0Y-vQ2VWJWCSIZTqjYoVZ3oFzf-CFos21S0F36q8al7SlmTJSEIZr82RGfhoW1M0cPvLl3IJkBfg2tHmNU4nx53xbHrPFdBy2o1MbZ1dHaJvgYAzRqE9xahxuFkdpGSG0jpLYRSvbFvhtjvQZ7kPvMJPBqD3Q0umuC7o2LBydkKTlhyb3duVWKyU8XQFmnaxggHhaUKZ4qU0zuAGV-2X4</recordid><startdate>20070701</startdate><enddate>20070701</enddate><creator>RONG, James X</creator><creator>YANG QIU</creator><creator>STRUM, Jay C</creator><creator>RYAN, Terence E</creator><creator>HANSEN, Michael K</creator><creator>LEI ZHU</creator><creator>ZHANG, Vivian</creator><creator>MI XIE</creator><creator>OKAMOTO, Yuji</creator><creator>MATTIE, Michael D</creator><creator>HIGASHIYAMA, Hiroyuki</creator><creator>ASANO, Satoshi</creator><general>American Diabetes Association</general><scope>IQODW</scope><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>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20070701</creationdate><title>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone</title><author>RONG, James X ; YANG QIU ; STRUM, Jay C ; RYAN, Terence E ; HANSEN, Michael K ; LEI ZHU ; ZHANG, Vivian ; MI XIE ; OKAMOTO, Yuji ; MATTIE, Michael D ; HIGASHIYAMA, Hiroyuki ; ASANO, Satoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-b9ffe12248769de8c638a417c4bf57ab6a14690394b8560ed9d39f1778d082033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue - drug effects</topic><topic>Adipose Tissue - metabolism</topic><topic>Adipose tissues</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biosynthesis</topic><topic>Body fat</topic><topic>Cytochrome</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet</topic><topic>Dietary Fats</topic><topic>Disease Models, Animal</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Gene Expression</topic><topic>Gene Expression Profiling</topic><topic>Genetic aspects</topic><topic>Glucose</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondrial DNA</topic><topic>Obesity</topic><topic>Obesity - drug therapy</topic><topic>PPAR gamma - agonists</topic><topic>Proteins</topic><topic>Risk factors</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Transcription factors</topic><topic>Transcription, Genetic</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RONG, James X</creatorcontrib><creatorcontrib>YANG QIU</creatorcontrib><creatorcontrib>STRUM, Jay C</creatorcontrib><creatorcontrib>RYAN, Terence E</creatorcontrib><creatorcontrib>HANSEN, Michael K</creatorcontrib><creatorcontrib>LEI ZHU</creatorcontrib><creatorcontrib>ZHANG, Vivian</creatorcontrib><creatorcontrib>MI XIE</creatorcontrib><creatorcontrib>OKAMOTO, Yuji</creatorcontrib><creatorcontrib>MATTIE, Michael D</creatorcontrib><creatorcontrib>HIGASHIYAMA, Hiroyuki</creatorcontrib><creatorcontrib>ASANO, Satoshi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Family Health Database (Proquest)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RONG, James X</au><au>YANG QIU</au><au>STRUM, Jay C</au><au>RYAN, Terence E</au><au>HANSEN, Michael K</au><au>LEI ZHU</au><au>ZHANG, Vivian</au><au>MI XIE</au><au>OKAMOTO, Yuji</au><au>MATTIE, Michael D</au><au>HIGASHIYAMA, Hiroyuki</au><au>ASANO, Satoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>56</volume><issue>7</issue><spage>1751</spage><epage>1760</epage><pages>1751-1760</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
James X. Rong 1 ,
Yang Qiu 2 3 ,
Michael K. Hansen 3 ,
Lei Zhu 3 4 ,
Vivian Zhang 3 ,
Mi Xie 1 ,
Yuji Okamoto 5 ,
Michael D. Mattie 6 ,
Hiroyuki Higashiyama 5 ,
Satoshi Asano 5 ,
Jay C. Strum 6 and
Terence E. Ryan 3
1 High Throughput Biology, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
2 Cheminformatics, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina
3 Integrative Biology, High Throughput Biology, Discovery Research, GlaxoSmithKline, King of Prussia, Pennsylvania
4 Biomedical Data Sciences, GlaxoSmithKline, Research Triangle Park, North Carolina
5 Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, Ibaraki, Japan
6 Department of Quantitative Expression, Genetics Research, GlaxoSmithKline, Research Triangle Park, North Carolina
Address correspondence and reprint requests to James X. Rong, High Throughput Biology, Discovery Research, GlaxoSmithKline,
5 Moore Dr., Research Triangle Park, NC. E-mail: james.x.rong{at}gsk.com
Abstract
The objective of this study was to further establish and confirm the relationship of adipose mitochondrial biogenesis in diabetes/obesity
and the effects of rosiglitazone (RSG), a peroxisome proliferator–activated receptor (PPAR) γ agonist, by systematically analyzing
mitochondrial gene expression and function in two mouse models of obesity and type 2 diabetes. Using microarray technology,
adipose mitochondrial gene transcription was studied in db/db , high-fat diet–fed C57BL/6 (HFD) and respective control mice with or without RSG treatment. The findings were extended using
mitochondrial staining, DNA quantification, and measurements of citrate synthase activity. In db/db and HFD mice, gene transcripts associated with mitochondrial ATP production, energy uncoupling, mitochondrial ribosomal proteins,
outer and inner membrane translocases, and mitochondrial heat-shock proteins were decreased in abundance, compared with db/+
and standard-fat diet–fed control mice, respectively. RSG dose-dependently increased these transcripts in both db/db and HFD mice and induced transcription of mitochondrial structural proteins and cellular antioxidant enzymes responsible
for removal of reactive oxygen species generated by increased mitochondrial activity. Transcription factors, including PPAR
coactivator (PGC)-1β, PGC-1α, estrogen-related receptor α, and PPARα, were suppressed in both models and induced by RSG. The
effects of RSG on adipose mitochondrial genes were confirmed by quantitative RT-PCR and further supported by mitochondrial
staining, mitochondrial DNA quantification, and citrate synthase activity. Adipose mitochondrial biogenesis was overwhelmingly
suppressed in both mouse models of diabetes/obesity and globally induced by RSG. These findings suggest an important role
of adipose mitochondria in diabetes/obesity and the potential for new treatment approaches targeting adipose mitochondria.
BAT, brown adipose tissue
CIDEA, cell death–inducing DFFA-like effector a
CPT, carnitinepalmitoyl transferase
FAO, fatty acid oxidation
HSP, heat-shock protein
OXPHOS, oxidative phosphorylation
PGC, PPAR coactivator
PPAR, peroxisome proliferator–activated receptor
RIP, receptor interacting protein
RSG, rosiglitazone
TCA, tricarboxylic acid
UCP, uncoupling protein
WAT, white adipose tissue
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 24 April 2007. DOI: 10.2337/db06-1135.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db06-1135 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted April 11, 2007.
Received August 14, 2006.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>17456854</pmid><doi>10.2337/db06-1135</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2007-07, Vol.56 (7), p.1751-1760 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_proquest_journals_216483961 |
| source | MEDLINE; PubMed Central; EZB Electronic Journals Library |
| subjects | Adipose tissue Adipose Tissue - drug effects Adipose Tissue - metabolism Adipose tissues Animals Biological and medical sciences Biosynthesis Body fat Cytochrome Diabetes Diabetes Mellitus, Type 2 - drug therapy Diabetes. Impaired glucose tolerance Diet Dietary Fats Disease Models, Animal Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Gene Expression Gene Expression Profiling Genetic aspects Glucose Hypoglycemic Agents - pharmacology Insulin Male Medical sciences Mice Mice, Inbred C57BL Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mitochondrial DNA Obesity Obesity - drug therapy PPAR gamma - agonists Proteins Risk factors Thiazolidinediones - pharmacology Transcription factors Transcription, Genetic Type 2 diabetes |
| title | Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone |
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