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
Hauptverfasser: Wong, Nicole, Fam, Barbara C, Cempako, Gitta R, Steinberg, Gregory R, Walder, Ken, Kay, Thomas W, Proietto, Joseph, Andrikopoulos, Sofianos
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container_end_page 3699
container_issue 10
container_start_page 3690
container_title Endocrinology (Philadelphia)
container_volume 152
creator Wong, Nicole
Fam, Barbara C
Cempako, Gitta R
Steinberg, Gregory R
Walder, Ken
Kay, Thomas W
Proietto, Joseph
Andrikopoulos, Sofianos
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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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&amp;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. 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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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