LACK OF ST2 ENHANCES HIGH-FAT DIET-INDUCED VISCERAL ADIPOSITY AND INFLAMMATION IN BALB/c MICE

  • Jelena Pantic Faculty of Medical Sciences University of Kragujevac
  • Nada Pejnovic Faculty of Medical Sciences University of Kragujevac
  • Gordana Radosavljevic Faculty of Medical Sciences University of Kragujevac
  • Ivan Jovanovic Faculty of Medical Sciences University of Kragujevac
  • Aleksandar Djukic Faculty of Medical Sciences University of Kragujevac
  • Nebojsa Arsenijevic Faculty of Medical Sciences University of Kragujevac
  • Miodrag Lukic Faculty of Medical Sciences University of Kragujevac

Sažetak


ABSTRACT

Obesity and obesity related disorders are strongly associated with chronic low-grade inflammation originating from growing visceral adipose tissue during nutrient excess. Although interleukin (IL)-33 may have protective role in obesity and atherosclerosis, the impact of IL-33/ST2 axis in metabolic disorders needs to be elucidated.

In this study, we investigated the role of IL-33/ST2 pathway in high-fat diet (HFD)-induced obesity using ST2-deficient (ST2-/-) and wild type mice on BALB/c background.

The deletion of ST2 enhanced systemic and visceral adipose tissue (VAT) inflammation and was associated with significantly higher weight gain and amount of total VAT in ST2-/- mice fed with HFD for 18 weeks. More numerous classically activated M1 macrophages and markedly decreased alternatively activated M2 macrophages were observed in VAT of HFD-fed ST2-/- mice. Additionally, VAT of ST2-/- mice fed with HFD had increased percentage of CD3+ T cells with lower incidence of CD4+CD25+FoxP3+ T regulatory cells in comparison with low-fat diet fed controls. The incidence of CD3+IL-17+ and IL-5 positive VAT-derived mononuclear cells was significantly lower in HFD-fed ST2-/- mice. Serum levels of proinflammatory cytokines IL-1β and IFN-γ were increased in HFD-fed ST2-/- mice, while the levels of IL-6 and CRP did not differ among groups. Importantly, the levels of anti-inflammatory IL-10 and IL-13 were significantly lower in the sera of ST2-/- mice compared with wild-type controls.

Our findings suggest that protective role of IL33/ST2 signaling in high-fat diet-induced adipose tissue inflammation. ST2 deficiency related to nutrient excess is associated with polarization of macrophages toward M1 phenotype and the induction Th1-mediated immune response.

Key words: ST2, obesity, high-fat diet, visceral adipose tissue, inflammation

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2014/02/26
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