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Publications (2)15.79 Total impact

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    ABSTRACT: Obesity elicits immune cells infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since Interleukin 21 (IL-21) plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Tregs differentiation/activity we hypothesized that it could play a role in obesity-induced insulin resistance.We found IL-21 and IL-21R mRNA expression up-regulated in adipose tissue of high fat diet WT mice and in stromal-vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (IL-21 KO) mice compared to WT animals fed both ND and HFD.In a context of diet-induced obesity, IL-21 KO mice, when compared to WT animals, exhibited lower body weight improved insulin sensitivity and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by an higher induction of IRF4, a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Tregs activity, developing and maintaining adipose tissue inflammation in the obesity state.
    Diabetes 01/2014; · 7.90 Impact Factor
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    ABSTRACT: Classically activated macrophages (M1) secrete pro-inflammatory cytokine and are predominant in obese adipose tissue. M2 macrophages, prevalent in lean adipose tissue, are induced by IL-13 and IL-4, mainly secreted by Th2 lymphocytes, and produce the anti-inflammatory cytokine IL-10. ITCH is a ubiquitously expressed E3 ubiquitin ligase involved in T cells differentiation and in a wide range of inflammatory pathways. ITCH down regulation in lymphocytes causes aberrant Th2 differentiation. To investigate the role of Th2 /M2 polarization in obesity-related inflammation and insulin resistance, we compared WT and Itch(-/-) mice in a context of diet-induced obesity (HFD). When subjected to HFD Itch(-/-) mice did not show increase in body weight and insulin resistance; calorimetric analysis suggested an accelerated metabolism. The molecular analysis of metabolically active tissue, revealed increased levels of M2 markers and genes involved in fatty acid oxidation. Histological examination of livers from Itch(-/-) mice suggest that ITCH deficiency protects mice from obesity related- NAFLD. We also found negative correlation between ITCH and M2 marker expression in human adipose tissues. Taken together, our data indicate that itch deficiency protects from the metabolic disorder caused by obesity.
    Diabetes 10/2013; · 7.90 Impact Factor