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Title: Deficiency in interferon-gamma results in reduced body weight and better glucose tolerance in mice.
Austin Authors: Wong, Nicole;Fam, Barbara C;Cempako, Gitta R;Steinberg, Gregory R;Walder, Ken;Kay, Thomas W;Proietto, Joseph ;Andrikopoulos, Sofianos
Affiliation: University of Melbourne, Department of Medicine (Austin Health and Northern Health), Heidelberg Repatriation Hospital, 300 Waterdale Road, Heidelberg Heights, Victoria 3081, Australia
Issue Date: 26-Jul-2011
Publication information: Endocrinology 2011; 152(10): 3690-9
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.
Gov't Doc #: 21791564
DOI: 10.1210/en.2011-0288
Type: Journal Article
Subjects: Animals
Body Weight
Liver Glycogen.metabolism
Mice, Inbred C57BL
Appears in Collections:Journal articles

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