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

Jelena Pantic; Nada Pejnovic; Gordana Radosavljevic; Ivan Jovanovic; Aleksandar Djukic; Nebojsa Arsenijevic; Miodrag Lukic

doi:10.5937/sjecr14-5243

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

DOI: https://doi.org/10.5937/sjecr14-5243

Abstract

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-typecontrols.

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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