Deficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice
Obesity is a chronic low-grade inflammatory disease caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even red...
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Veröffentlicht in: | Endocrinology (Philadelphia) 2011-10, Vol.152 (10), p.3690-3699 |
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description | Obesity is a chronic low-grade inflammatory disease caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly, more work is necessary to understand the role of cytokines on body weight control. The aim of this study was to determine the effect of interferon-γ deletion (IFNγ−/−) on body weight regulation and glucose metabolism. Male IFNγ−/− and wild-type C57BL/6 mice were fed a low-fat chow diet, and body weight, food intake, and energy expenditure were monitored over 20 wk. At the end of the study, ip glucose tolerance test, insulin tolerance test, basal glucose turnover, and hyperinsulinemic/euglycemic clamps were performed. Expression levels of arcuate nucleus neuropeptide Y, Agouti-related peptide, and proopiomelanocortin mRNA as well as circulating leptin levels were also determined. IFNγ−/− mice had improved glucose tolerance with reduced rate of glucose appearance and increased insulin sensitivity due to greater suppression of endogenous glucose output, which was associated with decreased hepatic glucose-6-phosphatase activity. In addition, we also observed reduced body weight associated with decreased food intake and increased physical activity. Neuropeptide Y and Agouti-related peptide mRNA expression was reduced, whereas proopiomelanocortin mRNA expression was increased, as were plasma leptin levels. Global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, improved glucose tolerance, and hepatic insulin sensitivity. Our findings demonstrate that IFNγ plays a critical role in the regulation of body weight and glucose metabolism. |
doi_str_mv | 10.1210/en.2011-0288 |
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Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly, more work is necessary to understand the role of cytokines on body weight control. The aim of this study was to determine the effect of interferon-γ deletion (IFNγ−/−) on body weight regulation and glucose metabolism. Male IFNγ−/− and wild-type C57BL/6 mice were fed a low-fat chow diet, and body weight, food intake, and energy expenditure were monitored over 20 wk. At the end of the study, ip glucose tolerance test, insulin tolerance test, basal glucose turnover, and hyperinsulinemic/euglycemic clamps were performed. Expression levels of arcuate nucleus neuropeptide Y, Agouti-related peptide, and proopiomelanocortin mRNA as well as circulating leptin levels were also determined. IFNγ−/− mice had improved glucose tolerance with reduced rate of glucose appearance and increased insulin sensitivity due to greater suppression of endogenous glucose output, which was associated with decreased hepatic glucose-6-phosphatase activity. In addition, we also observed reduced body weight associated with decreased food intake and increased physical activity. Neuropeptide Y and Agouti-related peptide mRNA expression was reduced, whereas proopiomelanocortin mRNA expression was increased, as were plasma leptin levels. Global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, improved glucose tolerance, and hepatic insulin sensitivity. Our findings demonstrate that IFNγ plays a critical role in the regulation of body weight and glucose metabolism.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2011-0288</identifier><identifier>PMID: 21791564</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Animal models ; Animals ; Arcuate nucleus ; Biological and medical sciences ; Body Weight ; Body weight gain ; Clamps ; Cytokines ; Deletion ; Energy balance ; Energy expenditure ; Energy intake ; Energy metabolism ; Food intake ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gluconeogenesis ; Glucose ; Glucose - metabolism ; Glucose tolerance ; Glucose-6-phosphatase ; Inflammatory diseases ; Insulin ; Interferon ; Interferon-gamma - physiology ; Leptin ; Liver ; Liver - metabolism ; Liver Glycogen - metabolism ; Low fat diet ; Male ; Metabolism ; Mice ; Mice, Inbred C57BL ; Neuropeptide Y ; Neuropeptides ; Nutrient deficiency ; Peptides ; Physical activity ; Proopiomelanocortin ; Sensitivity ; Vertebrates: endocrinology ; γ-Interferon</subject><ispartof>Endocrinology (Philadelphia), 2011-10, Vol.152 (10), p.3690-3699</ispartof><rights>Copyright © 2011 by The Endocrine Society</rights><rights>Copyright © 2011 by The Endocrine Society 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-8dff5d7505b49092dd0c7c1adf7cbdd2c5bdc0c226556e8a68f875692bc1ca13</citedby><cites>FETCH-LOGICAL-c462t-8dff5d7505b49092dd0c7c1adf7cbdd2c5bdc0c226556e8a68f875692bc1ca13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24567369$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21791564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Nicole</creatorcontrib><creatorcontrib>Fam, Barbara C</creatorcontrib><creatorcontrib>Cempako, Gitta R</creatorcontrib><creatorcontrib>Steinberg, Gregory R</creatorcontrib><creatorcontrib>Walder, Ken</creatorcontrib><creatorcontrib>Kay, Thomas W</creatorcontrib><creatorcontrib>Proietto, Joseph</creatorcontrib><creatorcontrib>Andrikopoulos, Sofianos</creatorcontrib><title>Deficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Obesity is a chronic low-grade inflammatory disease caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly, more work is necessary to understand the role of cytokines on body weight control. The aim of this study was to determine the effect of interferon-γ deletion (IFNγ−/−) on body weight regulation and glucose metabolism. Male IFNγ−/− and wild-type C57BL/6 mice were fed a low-fat chow diet, and body weight, food intake, and energy expenditure were monitored over 20 wk. At the end of the study, ip glucose tolerance test, insulin tolerance test, basal glucose turnover, and hyperinsulinemic/euglycemic clamps were performed. Expression levels of arcuate nucleus neuropeptide Y, Agouti-related peptide, and proopiomelanocortin mRNA as well as circulating leptin levels were also determined. IFNγ−/− mice had improved glucose tolerance with reduced rate of glucose appearance and increased insulin sensitivity due to greater suppression of endogenous glucose output, which was associated with decreased hepatic glucose-6-phosphatase activity. In addition, we also observed reduced body weight associated with decreased food intake and increased physical activity. Neuropeptide Y and Agouti-related peptide mRNA expression was reduced, whereas proopiomelanocortin mRNA expression was increased, as were plasma leptin levels. Global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, improved glucose tolerance, and hepatic insulin sensitivity. Our findings demonstrate that IFNγ plays a critical role in the regulation of body weight and glucose metabolism.</description><subject>Animal models</subject><subject>Animals</subject><subject>Arcuate nucleus</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Body weight gain</subject><subject>Clamps</subject><subject>Cytokines</subject><subject>Deletion</subject><subject>Energy balance</subject><subject>Energy expenditure</subject><subject>Energy intake</subject><subject>Energy metabolism</subject><subject>Food intake</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gluconeogenesis</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose tolerance</subject><subject>Glucose-6-phosphatase</subject><subject>Inflammatory diseases</subject><subject>Insulin</subject><subject>Interferon</subject><subject>Interferon-gamma - physiology</subject><subject>Leptin</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Liver Glycogen - metabolism</subject><subject>Low fat diet</subject><subject>Male</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neuropeptide Y</subject><subject>Neuropeptides</subject><subject>Nutrient deficiency</subject><subject>Peptides</subject><subject>Physical activity</subject><subject>Proopiomelanocortin</subject><subject>Sensitivity</subject><subject>Vertebrates: endocrinology</subject><subject>γ-Interferon</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1u1DAQgC0EokvhxhlFQogLKbYT_x2hQKlUhFStxNFyxmNIlbUXOznsc_EePFMT7cJKVXsajeabv4-Ql4yeMc7oe4xnnDJWU671I7JiphW1Yoo-JitKWVMrztUJeVbKzZy2bds8JSecKcOEbFfEfsLQQ48RdlUfq8s4Yg6YU6z__qmusUzDWJbCNfoJ0Fcfk99VP7D_-WusXJxzHOeO6mKYIBWs1mnA7CLg0vOtB3xOngQ3FHxxiKdk_eXz-vxrffX94vL8w1UNreRjrX0IwitBRdcaarj3FBQw54OCznsOovNAgXMphETtpA5aCWl4Bwwca07J2_3YbU6_Jyyj3fQFcBhcxDQVq01jlG4kncnXd8ibNOU432Yb1lBJNWVmpt7tKciplIzBbnO_cXlnGbWLdovRLtrton3GXx2GTt0G_X_4n-cZeHMAXAE3hMVRX45cK6RqpDn-kabtQyvrw8pmT2L0CXIfcZuxlOM39x56C4Dlpzs</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>Wong, Nicole</creator><creator>Fam, Barbara C</creator><creator>Cempako, Gitta R</creator><creator>Steinberg, Gregory R</creator><creator>Walder, Ken</creator><creator>Kay, Thomas W</creator><creator>Proietto, Joseph</creator><creator>Andrikopoulos, Sofianos</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20111001</creationdate><title>Deficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice</title><author>Wong, Nicole ; Fam, Barbara C ; Cempako, Gitta R ; Steinberg, Gregory R ; Walder, Ken ; Kay, Thomas W ; Proietto, Joseph ; Andrikopoulos, Sofianos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-8dff5d7505b49092dd0c7c1adf7cbdd2c5bdc0c226556e8a68f875692bc1ca13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Arcuate nucleus</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Body weight gain</topic><topic>Clamps</topic><topic>Cytokines</topic><topic>Deletion</topic><topic>Energy balance</topic><topic>Energy expenditure</topic><topic>Energy intake</topic><topic>Energy metabolism</topic><topic>Food intake</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Gluconeogenesis</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucose tolerance</topic><topic>Glucose-6-phosphatase</topic><topic>Inflammatory diseases</topic><topic>Insulin</topic><topic>Interferon</topic><topic>Interferon-gamma - physiology</topic><topic>Leptin</topic><topic>Liver</topic><topic>Liver - metabolism</topic><topic>Liver Glycogen - metabolism</topic><topic>Low fat diet</topic><topic>Male</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neuropeptide Y</topic><topic>Neuropeptides</topic><topic>Nutrient deficiency</topic><topic>Peptides</topic><topic>Physical activity</topic><topic>Proopiomelanocortin</topic><topic>Sensitivity</topic><topic>Vertebrates: endocrinology</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Nicole</creatorcontrib><creatorcontrib>Fam, Barbara C</creatorcontrib><creatorcontrib>Cempako, Gitta R</creatorcontrib><creatorcontrib>Steinberg, Gregory R</creatorcontrib><creatorcontrib>Walder, Ken</creatorcontrib><creatorcontrib>Kay, Thomas W</creatorcontrib><creatorcontrib>Proietto, Joseph</creatorcontrib><creatorcontrib>Andrikopoulos, Sofianos</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>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Nicole</au><au>Fam, Barbara C</au><au>Cempako, Gitta R</au><au>Steinberg, Gregory R</au><au>Walder, Ken</au><au>Kay, Thomas W</au><au>Proietto, Joseph</au><au>Andrikopoulos, Sofianos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>152</volume><issue>10</issue><spage>3690</spage><epage>3699</epage><pages>3690-3699</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Obesity is a chronic low-grade inflammatory disease caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of inflammatory cytokines have produced conflicting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly, more work is necessary to understand the role of cytokines on body weight control. The aim of this study was to determine the effect of interferon-γ deletion (IFNγ−/−) on body weight regulation and glucose metabolism. Male IFNγ−/− and wild-type C57BL/6 mice were fed a low-fat chow diet, and body weight, food intake, and energy expenditure were monitored over 20 wk. At the end of the study, ip glucose tolerance test, insulin tolerance test, basal glucose turnover, and hyperinsulinemic/euglycemic clamps were performed. Expression levels of arcuate nucleus neuropeptide Y, Agouti-related peptide, and proopiomelanocortin mRNA as well as circulating leptin levels were also determined. IFNγ−/− mice had improved glucose tolerance with reduced rate of glucose appearance and increased insulin sensitivity due to greater suppression of endogenous glucose output, which was associated with decreased hepatic glucose-6-phosphatase activity. In addition, we also observed reduced body weight associated with decreased food intake and increased physical activity. Neuropeptide Y and Agouti-related peptide mRNA expression was reduced, whereas proopiomelanocortin mRNA expression was increased, as were plasma leptin levels. Global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, improved glucose tolerance, and hepatic insulin sensitivity. Our findings demonstrate that IFNγ plays a critical role in the regulation of body weight and glucose metabolism.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>21791564</pmid><doi>10.1210/en.2011-0288</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
subjects | Animal models Animals Arcuate nucleus Biological and medical sciences Body Weight Body weight gain Clamps Cytokines Deletion Energy balance Energy expenditure Energy intake Energy metabolism Food intake Fundamental and applied biological sciences. Psychology Gene expression Gluconeogenesis Glucose Glucose - metabolism Glucose tolerance Glucose-6-phosphatase Inflammatory diseases Insulin Interferon Interferon-gamma - physiology Leptin Liver Liver - metabolism Liver Glycogen - metabolism Low fat diet Male Metabolism Mice Mice, Inbred C57BL Neuropeptide Y Neuropeptides Nutrient deficiency Peptides Physical activity Proopiomelanocortin Sensitivity Vertebrates: endocrinology γ-Interferon |
title | Deficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice |
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