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Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin resistance by regulating macrophage polarization.

Ying W, Kanameni S, Chang CA, Nair V, Safe S, Bazer FW, Zhou B - PLoS ONE (2014)

Bottom Line: Chronic adipose tissue inflammation is a hallmark of obesity-induced insulin resistance and anti-inflammatory agents can benefit patients with obesity-associated syndromes.Further investigations revealed that IFNT is a potent regulator of macrophage activation that favors anti-inflammatory responses as evidenced by activation of associated surface antigens, production of anti-inflammatory cytokines, and activation of selective cell signaling pathways.Thus, our study demonstrates, for the first time, that IFNT can significantly mitigate obesity-associated systemic insulin resistance and tissue inflammation by controlling macrophage polarization, and thus IFNT can be a novel bio-therapeutic agent for treating obesity-associated syndromes and type 2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science, Texas A&M University, College Station, Texas, United States of America.

ABSTRACT
Chronic adipose tissue inflammation is a hallmark of obesity-induced insulin resistance and anti-inflammatory agents can benefit patients with obesity-associated syndromes. Currently available type I interferons for therapeutic immunomodulation are accompanied by high cytotoxicity and therefore in this study we have examined anti-inflammatory effects of interferon tau (IFNT), a member of the type I interferon family with low cellular toxicity even at high doses. Using a diet-induced obesity mouse model, we observed enhanced insulin sensitivity in obese mice administered IFNT compared to control mice, which was accompanied by a significant decrease in secretion of proinflammatory cytokines and elevated anti-inflammatory macrophages (M2) in adipose tissue. Further investigations revealed that IFNT is a potent regulator of macrophage activation that favors anti-inflammatory responses as evidenced by activation of associated surface antigens, production of anti-inflammatory cytokines, and activation of selective cell signaling pathways. Thus, our study demonstrates, for the first time, that IFNT can significantly mitigate obesity-associated systemic insulin resistance and tissue inflammation by controlling macrophage polarization, and thus IFNT can be a novel bio-therapeutic agent for treating obesity-associated syndromes and type 2 diabetes.

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Interferon tau (IFNT) alleviates high-fat diet (HFD)-induced insulin resistance.Body weight (A) and food intake (B) of mice were monitored during a 12-week feeding period (n = 9–10). (C) Concentrations of glucose and insulin in plasma of control or IFNT-treated mice fed a HFD or low-fat diet (LFD), or fasted for 16 h. (D) Glucose tolerance test (n = 6). (E) Insulin tolerance test (n = 6). Data are presented as mean ± SEM. *P<0.05, **P<0.001, ***P<0.0001.
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pone-0098835-g001: Interferon tau (IFNT) alleviates high-fat diet (HFD)-induced insulin resistance.Body weight (A) and food intake (B) of mice were monitored during a 12-week feeding period (n = 9–10). (C) Concentrations of glucose and insulin in plasma of control or IFNT-treated mice fed a HFD or low-fat diet (LFD), or fasted for 16 h. (D) Glucose tolerance test (n = 6). (E) Insulin tolerance test (n = 6). Data are presented as mean ± SEM. *P<0.05, **P<0.001, ***P<0.0001.

Mentions: To evaluate the effects of IFNT on obesity-associated inflammation and insulin resistance, we adopted a dietary-induced obesity model. An effective IFNT dose was chosen based on previous studies [37]. After 12 weeks feeding, IFNT treatment did not significantly affect body weight gain or food intake in either HFD or LFD groups (Figure 1A, B). However, compared to the control HFD mice (HFD-Control mice), IFNT treatment (HFD-IFNT mice) decreased hyperglycemiaand blood insulin levels (Figure 1C). In addition, HFD-IFNT mice had lower glucose and insulin levels after 16-h of fasting compared to the HFD-Control mice (Figure 1C). To evaluate the effects of IFNT on insulin sensitivity, mice were subjected to glucose and insulin tolerance tests. Mice were fasted for 16 h and then injected with a single dose of glucose (2 mg of glucose per gram of body weight) or insulin (1 U of insulin per kg of body weight) followed by determination of concentrations of blood glucose at various time points (Figure 1D, E). With LFD mice, IFNT treatment did not alter concentrations of glucose or insulin in plasma; whereas HFD-IFNT mice had lower concentrations of glucose than HFD-Control mice (Figure 1D, E). Collectively, these results suggest that IFNT improves obesity-associated glucose metabolismand insulin sensitivity.


Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin resistance by regulating macrophage polarization.

Ying W, Kanameni S, Chang CA, Nair V, Safe S, Bazer FW, Zhou B - PLoS ONE (2014)

Interferon tau (IFNT) alleviates high-fat diet (HFD)-induced insulin resistance.Body weight (A) and food intake (B) of mice were monitored during a 12-week feeding period (n = 9–10). (C) Concentrations of glucose and insulin in plasma of control or IFNT-treated mice fed a HFD or low-fat diet (LFD), or fasted for 16 h. (D) Glucose tolerance test (n = 6). (E) Insulin tolerance test (n = 6). Data are presented as mean ± SEM. *P<0.05, **P<0.001, ***P<0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048269&req=5

pone-0098835-g001: Interferon tau (IFNT) alleviates high-fat diet (HFD)-induced insulin resistance.Body weight (A) and food intake (B) of mice were monitored during a 12-week feeding period (n = 9–10). (C) Concentrations of glucose and insulin in plasma of control or IFNT-treated mice fed a HFD or low-fat diet (LFD), or fasted for 16 h. (D) Glucose tolerance test (n = 6). (E) Insulin tolerance test (n = 6). Data are presented as mean ± SEM. *P<0.05, **P<0.001, ***P<0.0001.
Mentions: To evaluate the effects of IFNT on obesity-associated inflammation and insulin resistance, we adopted a dietary-induced obesity model. An effective IFNT dose was chosen based on previous studies [37]. After 12 weeks feeding, IFNT treatment did not significantly affect body weight gain or food intake in either HFD or LFD groups (Figure 1A, B). However, compared to the control HFD mice (HFD-Control mice), IFNT treatment (HFD-IFNT mice) decreased hyperglycemiaand blood insulin levels (Figure 1C). In addition, HFD-IFNT mice had lower glucose and insulin levels after 16-h of fasting compared to the HFD-Control mice (Figure 1C). To evaluate the effects of IFNT on insulin sensitivity, mice were subjected to glucose and insulin tolerance tests. Mice were fasted for 16 h and then injected with a single dose of glucose (2 mg of glucose per gram of body weight) or insulin (1 U of insulin per kg of body weight) followed by determination of concentrations of blood glucose at various time points (Figure 1D, E). With LFD mice, IFNT treatment did not alter concentrations of glucose or insulin in plasma; whereas HFD-IFNT mice had lower concentrations of glucose than HFD-Control mice (Figure 1D, E). Collectively, these results suggest that IFNT improves obesity-associated glucose metabolismand insulin sensitivity.

Bottom Line: Chronic adipose tissue inflammation is a hallmark of obesity-induced insulin resistance and anti-inflammatory agents can benefit patients with obesity-associated syndromes.Further investigations revealed that IFNT is a potent regulator of macrophage activation that favors anti-inflammatory responses as evidenced by activation of associated surface antigens, production of anti-inflammatory cytokines, and activation of selective cell signaling pathways.Thus, our study demonstrates, for the first time, that IFNT can significantly mitigate obesity-associated systemic insulin resistance and tissue inflammation by controlling macrophage polarization, and thus IFNT can be a novel bio-therapeutic agent for treating obesity-associated syndromes and type 2 diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science, Texas A&M University, College Station, Texas, United States of America.

ABSTRACT
Chronic adipose tissue inflammation is a hallmark of obesity-induced insulin resistance and anti-inflammatory agents can benefit patients with obesity-associated syndromes. Currently available type I interferons for therapeutic immunomodulation are accompanied by high cytotoxicity and therefore in this study we have examined anti-inflammatory effects of interferon tau (IFNT), a member of the type I interferon family with low cellular toxicity even at high doses. Using a diet-induced obesity mouse model, we observed enhanced insulin sensitivity in obese mice administered IFNT compared to control mice, which was accompanied by a significant decrease in secretion of proinflammatory cytokines and elevated anti-inflammatory macrophages (M2) in adipose tissue. Further investigations revealed that IFNT is a potent regulator of macrophage activation that favors anti-inflammatory responses as evidenced by activation of associated surface antigens, production of anti-inflammatory cytokines, and activation of selective cell signaling pathways. Thus, our study demonstrates, for the first time, that IFNT can significantly mitigate obesity-associated systemic insulin resistance and tissue inflammation by controlling macrophage polarization, and thus IFNT can be a novel bio-therapeutic agent for treating obesity-associated syndromes and type 2 diabetes.

Show MeSH
Related in: MedlinePlus