Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice
Abstract Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice...
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| Veröffentlicht in: | Metabolism, clinical and experimental clinical and experimental, 2012-08, Vol.61 (8), p.1152-1161 |
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| creator | O'Rourke, Robert W White, Ashley E Metcalf, Monja D Winters, Brian R Diggs, Brian S Zhu, Xinxia Marks, Daniel L |
| description | Abstract Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype. |
| doi_str_mv | 10.1016/j.metabol.2012.01.018 |
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IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.</description><identifier>ISSN: 0026-0495</identifier><identifier>EISSN: 1532-8600</identifier><identifier>DOI: 10.1016/j.metabol.2012.01.018</identifier><identifier>PMID: 22386937</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adipocytes - metabolism ; Adipocytes - pathology ; Adipogenesis ; Adipose Tissue - metabolism ; Adipose Tissue - pathology ; Animals ; Biological and medical sciences ; Cytokines - metabolism ; Diet, High-Fat ; Endocrinology & Metabolism ; Feeding. Feeding behavior ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Hypoglycemic Agents - metabolism ; Inflammation - metabolism ; Insulin - metabolism ; Insulin Resistance ; Interferon-gamma - deficiency ; Interferon-gamma - genetics ; Interferon-gamma - metabolism ; Intra-Abdominal Fat - metabolism ; Intra-Abdominal Fat - pathology ; Killer Cells, Natural - metabolism ; Killer Cells, Natural - pathology ; Lymphocytes ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Medical sciences ; Metabolic diseases ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Fluorescence ; Obesity ; Obesity - etiology ; Obesity - metabolism ; Phenotype ; Real-Time Polymerase Chain Reaction ; Subcutaneous Fat - metabolism ; Subcutaneous Fat - pathology ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Metabolism, clinical and experimental, 2012-08, Vol.61 (8), p.1152-1161</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>2012 Elsevier Inc. All rights reserved. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-4d2a37db2ae14db58b35181bb67afd84c36eff364be346d9b231ed721bf4a4ca3</citedby><cites>FETCH-LOGICAL-c552t-4d2a37db2ae14db58b35181bb67afd84c36eff364be346d9b231ed721bf4a4ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.metabol.2012.01.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26181233$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22386937$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O'Rourke, Robert W</creatorcontrib><creatorcontrib>White, Ashley E</creatorcontrib><creatorcontrib>Metcalf, Monja D</creatorcontrib><creatorcontrib>Winters, Brian R</creatorcontrib><creatorcontrib>Diggs, Brian S</creatorcontrib><creatorcontrib>Zhu, Xinxia</creatorcontrib><creatorcontrib>Marks, Daniel L</creatorcontrib><title>Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice</title><title>Metabolism, clinical and experimental</title><addtitle>Metabolism</addtitle><description>Abstract Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.</description><subject>Adipocytes - metabolism</subject><subject>Adipocytes - pathology</subject><subject>Adipogenesis</subject><subject>Adipose Tissue - metabolism</subject><subject>Adipose Tissue - pathology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cytokines - metabolism</subject><subject>Diet, High-Fat</subject><subject>Endocrinology & Metabolism</subject><subject>Feeding. Feeding behavior</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hypoglycemic Agents - metabolism</subject><subject>Inflammation - metabolism</subject><subject>Insulin - metabolism</subject><subject>Insulin Resistance</subject><subject>Interferon-gamma - deficiency</subject><subject>Interferon-gamma - genetics</subject><subject>Interferon-gamma - metabolism</subject><subject>Intra-Abdominal Fat - metabolism</subject><subject>Intra-Abdominal Fat - pathology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Killer Cells, Natural - pathology</subject><subject>Lymphocytes</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microscopy, Fluorescence</subject><subject>Obesity</subject><subject>Obesity - etiology</subject><subject>Obesity - metabolism</subject><subject>Phenotype</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Subcutaneous Fat - metabolism</subject><subject>Subcutaneous Fat - pathology</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>0026-0495</issn><issn>1532-8600</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktuFDEQhi0EIpPAEUC9QWLTg1_t9myCUEQgIoJFYG35UQ2e6baD7R5pzsU9ciY8miE8NkglWSp_9Vep_kLoGcFLgol4tV5OULSJ45JiQpeY1JAP0IJ0jLZSYPwQLTCmosV81Z2g05zXGOO-l-IxOqGUSbFi_QJ9uNnlApO3jQ_DqKdJFx9Do4OriTyPPjQZQvbFb33Z1VwTDWRori4_tnc_mk2IdhPn0lQFeIIeDXrM8PT4nqEvl28_X7xvrz-9u7p4c93arqOl5Y5q1jtDNRDuTCcN64gkxoheD05yywQMAxPcAOPCrQxlBFxPiRm45lazM3R-0L2dzQTOQihJj-o2-UmnnYraq79_gv-mvsatYrzrV5RUgZdHgRS_z5CLmny2MI46QJyzIpj2QhIheEW7A2pTzDnBcN-GYLU3Qq3V0Qi1N0JhUkPWuud_znhf9WvzFXhxBHS2ehySDtbn35yoK6GMVe71gYO60a2HpLL1ECw4n8AW5aL_7yjn_yjYaquvTTewg7yOcwrVLkVUrjXqZn81-6MhtB4MFz37CdONwMs</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>O'Rourke, Robert W</creator><creator>White, Ashley E</creator><creator>Metcalf, Monja D</creator><creator>Winters, Brian R</creator><creator>Diggs, Brian S</creator><creator>Zhu, Xinxia</creator><creator>Marks, Daniel L</creator><general>Elsevier Inc</general><general>Elsevier</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120801</creationdate><title>Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice</title><author>O'Rourke, Robert W ; White, Ashley E ; Metcalf, Monja D ; Winters, Brian R ; Diggs, Brian S ; Zhu, Xinxia ; Marks, Daniel L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-4d2a37db2ae14db58b35181bb67afd84c36eff364be346d9b231ed721bf4a4ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipocytes - metabolism</topic><topic>Adipocytes - pathology</topic><topic>Adipogenesis</topic><topic>Adipose Tissue - metabolism</topic><topic>Adipose Tissue - pathology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cytokines - metabolism</topic><topic>Diet, High-Fat</topic><topic>Endocrinology & Metabolism</topic><topic>Feeding. Feeding behavior</topic><topic>Flow Cytometry</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hypoglycemic Agents - metabolism</topic><topic>Inflammation - metabolism</topic><topic>Insulin - metabolism</topic><topic>Insulin Resistance</topic><topic>Interferon-gamma - deficiency</topic><topic>Interferon-gamma - genetics</topic><topic>Interferon-gamma - metabolism</topic><topic>Intra-Abdominal Fat - metabolism</topic><topic>Intra-Abdominal Fat - pathology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Killer Cells, Natural - pathology</topic><topic>Lymphocytes</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microscopy, Fluorescence</topic><topic>Obesity</topic><topic>Obesity - etiology</topic><topic>Obesity - metabolism</topic><topic>Phenotype</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Subcutaneous Fat - metabolism</topic><topic>Subcutaneous Fat - pathology</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O'Rourke, Robert W</creatorcontrib><creatorcontrib>White, Ashley E</creatorcontrib><creatorcontrib>Metcalf, Monja D</creatorcontrib><creatorcontrib>Winters, Brian R</creatorcontrib><creatorcontrib>Diggs, Brian S</creatorcontrib><creatorcontrib>Zhu, Xinxia</creatorcontrib><creatorcontrib>Marks, Daniel L</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Metabolism, clinical and experimental</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>O'Rourke, Robert W</au><au>White, Ashley E</au><au>Metcalf, Monja D</au><au>Winters, Brian R</au><au>Diggs, Brian S</au><au>Zhu, Xinxia</au><au>Marks, Daniel L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice</atitle><jtitle>Metabolism, clinical and experimental</jtitle><addtitle>Metabolism</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>61</volume><issue>8</issue><spage>1152</spage><epage>1161</epage><pages>1152-1161</pages><issn>0026-0495</issn><eissn>1532-8600</eissn><abstract>Abstract Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>22386937</pmid><doi>10.1016/j.metabol.2012.01.018</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adipocytes - metabolism Adipocytes - pathology Adipogenesis Adipose Tissue - metabolism Adipose Tissue - pathology Animals Biological and medical sciences Cytokines - metabolism Diet, High-Fat Endocrinology & Metabolism Feeding. Feeding behavior Flow Cytometry Fundamental and applied biological sciences. Psychology Hypoglycemic Agents - metabolism Inflammation - metabolism Insulin - metabolism Insulin Resistance Interferon-gamma - deficiency Interferon-gamma - genetics Interferon-gamma - metabolism Intra-Abdominal Fat - metabolism Intra-Abdominal Fat - pathology Killer Cells, Natural - metabolism Killer Cells, Natural - pathology Lymphocytes Macrophages - metabolism Macrophages - pathology Male Medical sciences Metabolic diseases Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Fluorescence Obesity Obesity - etiology Obesity - metabolism Phenotype Real-Time Polymerase Chain Reaction Subcutaneous Fat - metabolism Subcutaneous Fat - pathology Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice |
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