Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes
Aims/hypothesis Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages...
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| Veröffentlicht in: | Diabetologia 2012-09, Vol.55 (9), p.2456-2468 |
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| creator | Lee, Y.-S. Park, M.-S. Choung, J.-S. Kim, S.-S. Oh, H.-H. Choi, C.-S. Ha, S.-Y. Kang, Y. Kim, Y. Jun, H.-S. |
| description | Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity. |
| doi_str_mv | 10.1007/s00125-012-2592-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1093434763</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1093434763</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-cd6c6de213070ebef84f490ae7d5dcfcc4916f1db686aa84f54b6409675e43d83</originalsourceid><addsrcrecordid>eNqNkUtrFjEUhkNR7NfWH9BNCYjgJprbZGaWpWgrFNwodDdkkpOvqZnJNJlZCP54M87nBaHg5gTO-5xbXoTOGX3LKK3fZUoZr0gJhFctJ-II7ZgUnFDJm2dot8qENeruGJ3k_EApFZVUL9Ax5zXnsmI79P06LEbv40iC_wp4gmn2FgjDfrz3vZ8z1tZPMQOefc4L4EGbFKd7vYeCOB_mpGcfR6xHuyaCHoYt4dccjj2U2iEuP6OFgKPD1useZshn6LnTIcPLw3uKvnx4__nqhtx-uv54dXlLjKybmRirjLLAmaA1hR5cI51sqYbaVtY4Y2TLlGO2V43SuoiV7JWkraorkMI24hS92fpOKT4ukOdu8NlACHqEslnHaCukkLUS_4EKrgqvZEFf_YM-xCWN5ZCNEkq262y2UeXbck7guin5QadvBepWF7vNxa6EbnWxW5e4OHRe-gHs74pfthXg9QHQ2ejgkh6Nz384VTDBq8LxjctFGveQ_l7xqek_AJBdtRE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1032636498</pqid></control><display><type>article</type><title>Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Lee, Y.-S. ; Park, M.-S. ; Choung, J.-S. ; Kim, S.-S. ; Oh, H.-H. ; Choi, C.-S. ; Ha, S.-Y. ; Kang, Y. ; Kim, Y. ; Jun, H.-S.</creator><creatorcontrib>Lee, Y.-S. ; Park, M.-S. ; Choung, J.-S. ; Kim, S.-S. ; Oh, H.-H. ; Choi, C.-S. ; Ha, S.-Y. ; Kang, Y. ; Kim, Y. ; Jun, H.-S.</creatorcontrib><description>Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-012-2592-3</identifier><identifier>PMID: 22722451</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adenovirus ; Adenoviruses ; Adipocytes ; Adipose Tissue - metabolism ; Animals ; Anti-Inflammatory Agents - pharmacology ; Biological and medical sciences ; Body fat ; Body Fat Distribution ; Cytokines ; Diabetes ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Gene Expression Regulation ; Glucagon ; Glucagon-Like Peptide 1 - metabolism ; Glucagon-Like Peptide 1 - pharmacology ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Human Physiology ; Hypotheses ; Inflammation ; Inflammation - drug therapy ; Inflammation - metabolism ; Insulin Resistance ; Internal Medicine ; Kinases ; Macrophages - drug effects ; Macrophages - metabolism ; Medical research ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Mice ; Mice, Obese ; NF-kappa B - metabolism ; Obesity ; Obesity - metabolism ; Peptides ; Proteins ; Real-Time Polymerase Chain Reaction ; Receptors, Glucagon - metabolism</subject><ispartof>Diabetologia, 2012-09, Vol.55 (9), p.2456-2468</ispartof><rights>Springer-Verlag 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-cd6c6de213070ebef84f490ae7d5dcfcc4916f1db686aa84f54b6409675e43d83</citedby><cites>FETCH-LOGICAL-c478t-cd6c6de213070ebef84f490ae7d5dcfcc4916f1db686aa84f54b6409675e43d83</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/s00125-012-2592-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-012-2592-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26224325$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22722451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Y.-S.</creatorcontrib><creatorcontrib>Park, M.-S.</creatorcontrib><creatorcontrib>Choung, J.-S.</creatorcontrib><creatorcontrib>Kim, S.-S.</creatorcontrib><creatorcontrib>Oh, H.-H.</creatorcontrib><creatorcontrib>Choi, C.-S.</creatorcontrib><creatorcontrib>Ha, S.-Y.</creatorcontrib><creatorcontrib>Kang, Y.</creatorcontrib><creatorcontrib>Kim, Y.</creatorcontrib><creatorcontrib>Jun, H.-S.</creatorcontrib><title>Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.</description><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Adipocytes</subject><subject>Adipose Tissue - metabolism</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Body fat</subject><subject>Body Fat Distribution</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Gene Expression Regulation</subject><subject>Glucagon</subject><subject>Glucagon-Like Peptide 1 - metabolism</subject><subject>Glucagon-Like Peptide 1 - pharmacology</subject><subject>Glucagon-Like Peptide-1 Receptor</subject><subject>Glucose</subject><subject>Human Physiology</subject><subject>Hypotheses</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - metabolism</subject><subject>Insulin Resistance</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Obese</subject><subject>NF-kappa B - metabolism</subject><subject>Obesity</subject><subject>Obesity - metabolism</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Glucagon - metabolism</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkUtrFjEUhkNR7NfWH9BNCYjgJprbZGaWpWgrFNwodDdkkpOvqZnJNJlZCP54M87nBaHg5gTO-5xbXoTOGX3LKK3fZUoZr0gJhFctJ-II7ZgUnFDJm2dot8qENeruGJ3k_EApFZVUL9Ax5zXnsmI79P06LEbv40iC_wp4gmn2FgjDfrz3vZ8z1tZPMQOefc4L4EGbFKd7vYeCOB_mpGcfR6xHuyaCHoYt4dccjj2U2iEuP6OFgKPD1useZshn6LnTIcPLw3uKvnx4__nqhtx-uv54dXlLjKybmRirjLLAmaA1hR5cI51sqYbaVtY4Y2TLlGO2V43SuoiV7JWkraorkMI24hS92fpOKT4ukOdu8NlACHqEslnHaCukkLUS_4EKrgqvZEFf_YM-xCWN5ZCNEkq262y2UeXbck7guin5QadvBepWF7vNxa6EbnWxW5e4OHRe-gHs74pfthXg9QHQ2ejgkh6Nz384VTDBq8LxjctFGveQ_l7xqek_AJBdtRE</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Lee, Y.-S.</creator><creator>Park, M.-S.</creator><creator>Choung, J.-S.</creator><creator>Kim, S.-S.</creator><creator>Oh, H.-H.</creator><creator>Choi, C.-S.</creator><creator>Ha, S.-Y.</creator><creator>Kang, Y.</creator><creator>Kim, Y.</creator><creator>Jun, H.-S.</creator><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20120901</creationdate><title>Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes</title><author>Lee, Y.-S. ; Park, M.-S. ; Choung, J.-S. ; Kim, S.-S. ; Oh, H.-H. ; Choi, C.-S. ; Ha, S.-Y. ; Kang, Y. ; Kim, Y. ; Jun, H.-S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-cd6c6de213070ebef84f490ae7d5dcfcc4916f1db686aa84f54b6409675e43d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenovirus</topic><topic>Adenoviruses</topic><topic>Adipocytes</topic><topic>Adipose Tissue - metabolism</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Body fat</topic><topic>Body Fat Distribution</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Gene Expression Regulation</topic><topic>Glucagon</topic><topic>Glucagon-Like Peptide 1 - metabolism</topic><topic>Glucagon-Like Peptide 1 - pharmacology</topic><topic>Glucagon-Like Peptide-1 Receptor</topic><topic>Glucose</topic><topic>Human Physiology</topic><topic>Hypotheses</topic><topic>Inflammation</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - metabolism</topic><topic>Insulin Resistance</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Obese</topic><topic>NF-kappa B - metabolism</topic><topic>Obesity</topic><topic>Obesity - metabolism</topic><topic>Peptides</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Glucagon - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Y.-S.</creatorcontrib><creatorcontrib>Park, M.-S.</creatorcontrib><creatorcontrib>Choung, J.-S.</creatorcontrib><creatorcontrib>Kim, S.-S.</creatorcontrib><creatorcontrib>Oh, H.-H.</creatorcontrib><creatorcontrib>Choi, C.-S.</creatorcontrib><creatorcontrib>Ha, S.-Y.</creatorcontrib><creatorcontrib>Kang, Y.</creatorcontrib><creatorcontrib>Kim, Y.</creatorcontrib><creatorcontrib>Jun, H.-S.</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>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Y.-S.</au><au>Park, M.-S.</au><au>Choung, J.-S.</au><au>Kim, S.-S.</au><au>Oh, H.-H.</au><au>Choi, C.-S.</au><au>Ha, S.-Y.</au><au>Kang, Y.</au><au>Kim, Y.</au><au>Jun, H.-S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2012-09-01</date><risdate>2012</risdate><volume>55</volume><issue>9</issue><spage>2456</spage><epage>2468</epage><pages>2456-2468</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>22722451</pmid><doi>10.1007/s00125-012-2592-3</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Diabetologia, 2012-09, Vol.55 (9), p.2456-2468 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1093434763 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adenovirus Adenoviruses Adipocytes Adipose Tissue - metabolism Animals Anti-Inflammatory Agents - pharmacology Biological and medical sciences Body fat Body Fat Distribution Cytokines Diabetes Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Gene Expression Regulation Glucagon Glucagon-Like Peptide 1 - metabolism Glucagon-Like Peptide 1 - pharmacology Glucagon-Like Peptide-1 Receptor Glucose Human Physiology Hypotheses Inflammation Inflammation - drug therapy Inflammation - metabolism Insulin Resistance Internal Medicine Kinases Macrophages - drug effects Macrophages - metabolism Medical research Medical sciences Medicine Medicine & Public Health Metabolic Diseases Metabolism Mice Mice, Obese NF-kappa B - metabolism Obesity Obesity - metabolism Peptides Proteins Real-Time Polymerase Chain Reaction Receptors, Glucagon - metabolism |
| title | Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes |
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