Deficiency in Interferon-γ Results in Reduced Body Weight and Better Glucose Tolerance in Mice

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.

Insulin Response Genes in Different Stages of Periodontal Disease

“…The increased INFG mRNA is a clear sign for inductions of gingival inflammation, since interferon γ is an activator for both innate and adaptive immunity. Wong et al (2011) demonstrated that restricting interferon γ in mice improved their glucose metabolism. There was also a significant increase in CEBPA, which encodes for CCAAT/enhancer-binding protein α that controls transcriptions of GCSF and IL6R genes and therefore affects granulocytes differentiation (Zhang et al 1998).…”

The influence of leptin on Th1/Th2 balance in obese children with asthma

“…(12) The cytokine IFN-γ, which is predominantly derived from T cells and natural killer T cells, (13) plays an important role in the innate and adaptive immune responses, particularly regarding viral infections. Because IFN-γ is primarily secreted by T cells and natural killer T cells, (14) emerging evidence suggests that increases in the T-cell population in adipose tissue and leptin modulation of T cells to a Th1 immune response, with increased production of IFN-γ, (12,14) contribute to obesity in subjects with a specific asthma phenotype.…”

What Is the Role of Inflammatory Mediators on Energy Metabolism?

“…Precisely because the IFN-γ is high in obesity, studies suggest that this cytokine impairs glucose homeostasis and body weight control [8][9][10] .…”

“…It has been shown that during obesity, elevated concentrations of IFN-γ favor the body weight gain and impair the glucose homeostasis [8][9][10] . However, the suppression of this mediator promotes inverse effect.…”

“…However, the suppression of this mediator promotes inverse effect. It favors the body weight reduction and improves of insulin sensitivity, since the absence of such mediator promotes the REVIEW decreased food intake, suppressing the orexigenic and stimulating the anorexigenic route [8] . So, it is plausible to infer that there is correlation between such mediator and mechanisms which alter the energy metabolism.…”