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Title: ST2 deficiency ameliorates high fat diet-induced liver steatosis in BALB/c mice
Authors: Jovicic, Nemanja
Jeftic, Ilija
Miletic Kovacevic, Marina
Tanaskovic, Irena
Arsenijevic, Nebojsa
Lukic, Miodrag
Pejnović, Nada
Issue Date: 2015
Abstract: © 2015 University of Kragujevac, Faculty of Science. All right reserved. Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but the molecular mechanisms of liver steatosis and its progression to non-alcoholic steatohepatitis and fibrosis are incompletely understood. Immune reactivity plays an important role in the pathogenesis of NAFLD. The IL-33/ST2 axis has a protective role in adiposity and atherosclerosis, but its role in obesity-associated metabolic disorders requires further clarification. To investigate the unresolved role of IL-33/ST2 signalling in NAFLD, we used ST2-deficient (ST2-/-) and wild type (WT) BALB/c mice maintained on a high-fat diet (HFD) for 24 weeks. HFDfed ST2-/- mice exhibited increased weight gain, visceral adipose tissue weight and triglyceridaemia and decreased liver weight compared with diet-matched WT mice. Compared with WT mice on an HFD, ST2 deletion significantly reduced hepatic steatosis, liver inflammation and fibrosis and downregulated the expression of genes related to lipid metabolism in the liver. The frequency of innate immune cells in the liver, including CD68+ macrophages and CD11c+ dendritic cells, was lower in HFD-fed ST2-/- mice, accompanied by lower TNFα serum levels compared with dietmatched WT mice. Less collagen deposition in the livers of ST2-/- mice on an HFD was associated with lower numbers of profibrotic CD11b+Ly6clow monocytes and CD4+IL-17+ T cells in the liver, lower hepatic gene expression of procollagen, IL-33 and IL-13, and lower serum levels of IL-33 and IL-13 compared with diet-matched WT mice. Our findings suggest that the IL-33/ST2 axis may have a complex role in obesity-associated metabolic disorders. Although it is protective in HFD-induced adiposity, the IL-33/ ST2 pathway promotes hepatic steatosis, inflammation and fibrosis.
Type: article
DOI: 10.1515/SJECR-2015-0002
ISSN: 1820-8665
SCOPUS: 2-s2.0-84925934671
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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