GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance
Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhoo...
Gespeichert in:
| Veröffentlicht in: | PloS one 2014-10, Vol.9 (10), p.e109540-e109540 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e109540 |
|---|---|
| container_issue | 10 |
| container_start_page | e109540 |
| container_title | PloS one |
| container_volume | 9 |
| creator | Favaretto, Francesca Milan, Gabriella Collin, Gayle B Marshall, Jan D Stasi, Fabio Maffei, Pietro Vettor, Roberto Naggert, Jürgen K |
| description | Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced insulin-stimulated glucose uptake. Assessment of whole body glucose homeostasis revealed glucose intolerance. Insulin stimulation resulted in proper AKT phosphorylation in adipose tissue. However, the total amount of glucose transporter 4 (SLC4A2) and its translocation to the plasma membrane were reduced in mutant adipose depots compared to wildtype littermates. Alterations in insulin stimulated trafficking of glucose transporter 4 are an early sign of metabolic dysfunction in Alström mutant mice, providing a possible explanation for the reduced glucose uptake and the compensatory hyperinsulinemia. The metabolic signaling deficits either reside downstream or are independent of AKT activation and suggest a role for ALMS1 in GLUT4 trafficking. Alström mutant mice represent an interesting model for the development of metabolic disease in which adipose tissue with a reduced glucose uptake can expand by de novo lipogenesis to an obese state. |
| doi_str_mv | 10.1371/journal.pone.0109540 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1609504131</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_799ff5044e734e85b48807b54c907445</doaj_id><sourcerecordid>1610755362</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4410-4116d7b085a79f4564ac7789cb45928e60261e12cb70346a6c7ee259c70f81373</originalsourceid><addsrcrecordid>eNptUk1r3DAQNaWlSdP-g9IKesmhu5GsL-tSCCHdBhZ62ZyFLI-3WmRpK9mB_Qf92VWyTkhKTzOM3nuaebyq-kjwklBJLnZxSsH45T4GWGKCFWf4VXVKFK0Xosb09bP-pHqX8w5jThsh3lYnNa-VEpKcVn9W69sNQx30YMeMXECmc_uYAY0u5wmQSYDAJH9A2W1DRrFHA4ymjd5ZZPwIyYwuhgfqpR8yWW0uVpuvyKAhTkVmiB141MeEYgvZjQdkQlfAefKFkcoojyZYeF-96Y3P8GGuZ9Xt9-vN1Y_F-ufq5upyvbCMEbxghIhOtrjhRqqeccGMlbJRtmVc1Q0IXAsCpLatxJQJI6wEqLmyEvdN8Y2eVZ-Punsfs55NzJqIYiBmhJKCuDkiumh2ep_cYNJBR-P0wyCmrTZpdNaDlkr1faExkJRBw1vWNFi2nFmFJWO8aH2bf5vaAToLYUzGvxB9-RLcL72Nd5oRVVNOi8D5LJDi7wnyqAeXLXhvAhR_y94ES86pqAv0yz_Q_1_HjiibYs4J-qdlCNb3wXpk6ftg6TlYhfbp-SFPpMck0b-kpsqY</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1609504131</pqid></control><display><type>article</type><title>GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Favaretto, Francesca ; Milan, Gabriella ; Collin, Gayle B ; Marshall, Jan D ; Stasi, Fabio ; Maffei, Pietro ; Vettor, Roberto ; Naggert, Jürgen K</creator><contributor>Eckel, Juergen</contributor><creatorcontrib>Favaretto, Francesca ; Milan, Gabriella ; Collin, Gayle B ; Marshall, Jan D ; Stasi, Fabio ; Maffei, Pietro ; Vettor, Roberto ; Naggert, Jürgen K ; Eckel, Juergen</creatorcontrib><description>Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced insulin-stimulated glucose uptake. Assessment of whole body glucose homeostasis revealed glucose intolerance. Insulin stimulation resulted in proper AKT phosphorylation in adipose tissue. However, the total amount of glucose transporter 4 (SLC4A2) and its translocation to the plasma membrane were reduced in mutant adipose depots compared to wildtype littermates. Alterations in insulin stimulated trafficking of glucose transporter 4 are an early sign of metabolic dysfunction in Alström mutant mice, providing a possible explanation for the reduced glucose uptake and the compensatory hyperinsulinemia. The metabolic signaling deficits either reside downstream or are independent of AKT activation and suggest a role for ALMS1 in GLUT4 trafficking. Alström mutant mice represent an interesting model for the development of metabolic disease in which adipose tissue with a reduced glucose uptake can expand by de novo lipogenesis to an obese state.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0109540</identifier><identifier>PMID: 25299671</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipocytes ; Adipocytes - drug effects ; Adipocytes - metabolism ; Adipocytes - pathology ; Adipogenesis - genetics ; Adipose tissue ; Adipose Tissue - metabolism ; Adipose Tissue - pathology ; AKT protein ; Alstrom Syndrome - genetics ; Alstrom Syndrome - metabolism ; Alstrom Syndrome - pathology ; Animal models ; Animals ; Biological Transport ; Biology and Life Sciences ; Body fat ; Body Weight ; Cell Cycle Proteins ; Children ; Chloride-Bicarbonate Antiporters - genetics ; Chloride-Bicarbonate Antiporters - metabolism ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Disease Models, Animal ; DNA-Binding Proteins - deficiency ; DNA-Binding Proteins - genetics ; Eutrophication ; Gene Expression Regulation ; Glucose ; Glucose - metabolism ; Glucose Intolerance ; Glucose tolerance ; Glucose transporter ; Homeostasis ; Humans ; Hyperinsulinemia ; Hyperinsulinism - genetics ; Hyperinsulinism - metabolism ; Hyperinsulinism - pathology ; Insertion ; Insulin ; Insulin - metabolism ; Insulin - pharmacology ; Insulin Resistance ; Intolerance ; Lipogenesis ; Male ; Medicine and Health Sciences ; Metabolic disorders ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutants ; Mutation ; Obesity ; Phosphorylation ; Primary Cell Culture ; Rodents ; Signal Transduction ; Signaling ; Translocation</subject><ispartof>PloS one, 2014-10, Vol.9 (10), p.e109540-e109540</ispartof><rights>2014 Favaretto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Favaretto et al 2014 Favaretto et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4410-4116d7b085a79f4564ac7789cb45928e60261e12cb70346a6c7ee259c70f81373</citedby><cites>FETCH-LOGICAL-c4410-4116d7b085a79f4564ac7789cb45928e60261e12cb70346a6c7ee259c70f81373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192353/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192353/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25299671$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Eckel, Juergen</contributor><creatorcontrib>Favaretto, Francesca</creatorcontrib><creatorcontrib>Milan, Gabriella</creatorcontrib><creatorcontrib>Collin, Gayle B</creatorcontrib><creatorcontrib>Marshall, Jan D</creatorcontrib><creatorcontrib>Stasi, Fabio</creatorcontrib><creatorcontrib>Maffei, Pietro</creatorcontrib><creatorcontrib>Vettor, Roberto</creatorcontrib><creatorcontrib>Naggert, Jürgen K</creatorcontrib><title>GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced insulin-stimulated glucose uptake. Assessment of whole body glucose homeostasis revealed glucose intolerance. Insulin stimulation resulted in proper AKT phosphorylation in adipose tissue. However, the total amount of glucose transporter 4 (SLC4A2) and its translocation to the plasma membrane were reduced in mutant adipose depots compared to wildtype littermates. Alterations in insulin stimulated trafficking of glucose transporter 4 are an early sign of metabolic dysfunction in Alström mutant mice, providing a possible explanation for the reduced glucose uptake and the compensatory hyperinsulinemia. The metabolic signaling deficits either reside downstream or are independent of AKT activation and suggest a role for ALMS1 in GLUT4 trafficking. Alström mutant mice represent an interesting model for the development of metabolic disease in which adipose tissue with a reduced glucose uptake can expand by de novo lipogenesis to an obese state.</description><subject>Adipocytes</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Adipocytes - pathology</subject><subject>Adipogenesis - genetics</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose Tissue - pathology</subject><subject>AKT protein</subject><subject>Alstrom Syndrome - genetics</subject><subject>Alstrom Syndrome - metabolism</subject><subject>Alstrom Syndrome - pathology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Biology and Life Sciences</subject><subject>Body fat</subject><subject>Body Weight</subject><subject>Cell Cycle Proteins</subject><subject>Children</subject><subject>Chloride-Bicarbonate Antiporters - genetics</subject><subject>Chloride-Bicarbonate Antiporters - metabolism</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Disease Models, Animal</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Eutrophication</subject><subject>Gene Expression Regulation</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose Intolerance</subject><subject>Glucose tolerance</subject><subject>Glucose transporter</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Hyperinsulinemia</subject><subject>Hyperinsulinism - genetics</subject><subject>Hyperinsulinism - metabolism</subject><subject>Hyperinsulinism - pathology</subject><subject>Insertion</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin - pharmacology</subject><subject>Insulin Resistance</subject><subject>Intolerance</subject><subject>Lipogenesis</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metabolic disorders</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Obesity</subject><subject>Phosphorylation</subject><subject>Primary Cell Culture</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Translocation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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><sourceid>DOA</sourceid><recordid>eNptUk1r3DAQNaWlSdP-g9IKesmhu5GsL-tSCCHdBhZ62ZyFLI-3WmRpK9mB_Qf92VWyTkhKTzOM3nuaebyq-kjwklBJLnZxSsH45T4GWGKCFWf4VXVKFK0Xosb09bP-pHqX8w5jThsh3lYnNa-VEpKcVn9W69sNQx30YMeMXECmc_uYAY0u5wmQSYDAJH9A2W1DRrFHA4ymjd5ZZPwIyYwuhgfqpR8yWW0uVpuvyKAhTkVmiB141MeEYgvZjQdkQlfAefKFkcoojyZYeF-96Y3P8GGuZ9Xt9-vN1Y_F-ufq5upyvbCMEbxghIhOtrjhRqqeccGMlbJRtmVc1Q0IXAsCpLatxJQJI6wEqLmyEvdN8Y2eVZ-Punsfs55NzJqIYiBmhJKCuDkiumh2ep_cYNJBR-P0wyCmrTZpdNaDlkr1faExkJRBw1vWNFi2nFmFJWO8aH2bf5vaAToLYUzGvxB9-RLcL72Nd5oRVVNOi8D5LJDi7wnyqAeXLXhvAhR_y94ES86pqAv0yz_Q_1_HjiibYs4J-qdlCNb3wXpk6ftg6TlYhfbp-SFPpMck0b-kpsqY</recordid><startdate>20141009</startdate><enddate>20141009</enddate><creator>Favaretto, Francesca</creator><creator>Milan, Gabriella</creator><creator>Collin, Gayle B</creator><creator>Marshall, Jan D</creator><creator>Stasi, Fabio</creator><creator>Maffei, Pietro</creator><creator>Vettor, Roberto</creator><creator>Naggert, Jürgen K</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141009</creationdate><title>GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance</title><author>Favaretto, Francesca ; Milan, Gabriella ; Collin, Gayle B ; Marshall, Jan D ; Stasi, Fabio ; Maffei, Pietro ; Vettor, Roberto ; Naggert, Jürgen K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4410-4116d7b085a79f4564ac7789cb45928e60261e12cb70346a6c7ee259c70f81373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adipocytes</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Adipocytes - pathology</topic><topic>Adipogenesis - genetics</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - metabolism</topic><topic>Adipose Tissue - pathology</topic><topic>AKT protein</topic><topic>Alstrom Syndrome - genetics</topic><topic>Alstrom Syndrome - metabolism</topic><topic>Alstrom Syndrome - pathology</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Biology and Life Sciences</topic><topic>Body fat</topic><topic>Body Weight</topic><topic>Cell Cycle Proteins</topic><topic>Children</topic><topic>Chloride-Bicarbonate Antiporters - genetics</topic><topic>Chloride-Bicarbonate Antiporters - metabolism</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Disease Models, Animal</topic><topic>DNA-Binding Proteins - deficiency</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Eutrophication</topic><topic>Gene Expression Regulation</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucose Intolerance</topic><topic>Glucose tolerance</topic><topic>Glucose transporter</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Hyperinsulinemia</topic><topic>Hyperinsulinism - genetics</topic><topic>Hyperinsulinism - metabolism</topic><topic>Hyperinsulinism - pathology</topic><topic>Insertion</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin - pharmacology</topic><topic>Insulin Resistance</topic><topic>Intolerance</topic><topic>Lipogenesis</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Metabolic disorders</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Obesity</topic><topic>Phosphorylation</topic><topic>Primary Cell Culture</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Favaretto, Francesca</creatorcontrib><creatorcontrib>Milan, Gabriella</creatorcontrib><creatorcontrib>Collin, Gayle B</creatorcontrib><creatorcontrib>Marshall, Jan D</creatorcontrib><creatorcontrib>Stasi, Fabio</creatorcontrib><creatorcontrib>Maffei, Pietro</creatorcontrib><creatorcontrib>Vettor, Roberto</creatorcontrib><creatorcontrib>Naggert, Jürgen K</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</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</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Favaretto, Francesca</au><au>Milan, Gabriella</au><au>Collin, Gayle B</au><au>Marshall, Jan D</au><au>Stasi, Fabio</au><au>Maffei, Pietro</au><au>Vettor, Roberto</au><au>Naggert, Jürgen K</au><au>Eckel, Juergen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-10-09</date><risdate>2014</risdate><volume>9</volume><issue>10</issue><spage>e109540</spage><epage>e109540</epage><pages>e109540-e109540</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced insulin-stimulated glucose uptake. Assessment of whole body glucose homeostasis revealed glucose intolerance. Insulin stimulation resulted in proper AKT phosphorylation in adipose tissue. However, the total amount of glucose transporter 4 (SLC4A2) and its translocation to the plasma membrane were reduced in mutant adipose depots compared to wildtype littermates. Alterations in insulin stimulated trafficking of glucose transporter 4 are an early sign of metabolic dysfunction in Alström mutant mice, providing a possible explanation for the reduced glucose uptake and the compensatory hyperinsulinemia. The metabolic signaling deficits either reside downstream or are independent of AKT activation and suggest a role for ALMS1 in GLUT4 trafficking. Alström mutant mice represent an interesting model for the development of metabolic disease in which adipose tissue with a reduced glucose uptake can expand by de novo lipogenesis to an obese state.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25299671</pmid><doi>10.1371/journal.pone.0109540</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-10, Vol.9 (10), p.e109540-e109540 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1609504131 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adipocytes Adipocytes - drug effects Adipocytes - metabolism Adipocytes - pathology Adipogenesis - genetics Adipose tissue Adipose Tissue - metabolism Adipose Tissue - pathology AKT protein Alstrom Syndrome - genetics Alstrom Syndrome - metabolism Alstrom Syndrome - pathology Animal models Animals Biological Transport Biology and Life Sciences Body fat Body Weight Cell Cycle Proteins Children Chloride-Bicarbonate Antiporters - genetics Chloride-Bicarbonate Antiporters - metabolism Diabetes mellitus Diabetes mellitus (non-insulin dependent) Disease Models, Animal DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics Eutrophication Gene Expression Regulation Glucose Glucose - metabolism Glucose Intolerance Glucose tolerance Glucose transporter Homeostasis Humans Hyperinsulinemia Hyperinsulinism - genetics Hyperinsulinism - metabolism Hyperinsulinism - pathology Insertion Insulin Insulin - metabolism Insulin - pharmacology Insulin Resistance Intolerance Lipogenesis Male Medicine and Health Sciences Metabolic disorders Mice Mice, Inbred C57BL Mice, Transgenic Mutants Mutation Obesity Phosphorylation Primary Cell Culture Rodents Signal Transduction Signaling Translocation |
| title | GLUT4 defects in adipose tissue are early signs of metabolic alterations in Alms1GT/GT, a mouse model for obesity and insulin resistance |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T15%3A30%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=GLUT4%20defects%20in%20adipose%20tissue%20are%20early%20signs%20of%20metabolic%20alterations%20in%20Alms1GT/GT,%20a%20mouse%20model%20for%20obesity%20and%20insulin%20resistance&rft.jtitle=PloS%20one&rft.au=Favaretto,%20Francesca&rft.date=2014-10-09&rft.volume=9&rft.issue=10&rft.spage=e109540&rft.epage=e109540&rft.pages=e109540-e109540&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0109540&rft_dat=%3Cproquest_plos_%3E1610755362%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1609504131&rft_id=info:pmid/25299671&rft_doaj_id=oai_doaj_org_article_799ff5044e734e85b48807b54c907445&rfr_iscdi=true |