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Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice

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Title: Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice
Author(s): Pini, Maria; Rhodes, Davina H.; Fantuzzi, Giamila
Subject(s): obesity inflammation acute-phase response platelets leukocytes
Abstract: Obesity is associated with chronic inflammation and elevated levels of IL-6. The role of IL-6 in induction of acute-phase proteins and modulation of haematological responses has been demonstrated in models of inflammation and aging, but not in obesity. We hypothesized that IL-6 is necessary to regulate the acute-phase response and hematological changes associated with diet-induced obesity (DIO) in mice. Feeding a 60% kcal/fat diet for 13 weeks to C57BL6 WT male mice induced a significant increase in IL-6 expression in visceral adipose tissue (VAT), but not liver, compared to mice fed chow diet. Significantly elevated IL-6 levels were present in the peritoneal lavage fluid, but not plasma, of DIO compared to lean mice. A comparable degree of obesity, hepatomegaly, hyperleptinemia, VAT inflammation and insulin resistance was observed in DIO WT and IL-6 KO mice compared to WT and KO mice fed chow diet. Significant leukocytosis was observed in DIO WT but not DIO KO mice compared to lean groups. A significant reduction in platelet counts, without alterations in platelet size, percentage of circulating reticulated platelets and number of bone marrow megakaryocytes, was present in DIO KO mice compared to each other group. Hepatic expression of thrombopoietin was comparable in each group, with DIO WT and KO mice having reduced VAT expression compared to lean mice. Lean KO mice had significantly elevated plasma levels of thrombopoietin compared to each other group, whereas liver-associated thrombopoietin levels were comparable in each group. Deficiency of IL-6 resulted in blunted hepatic induction of the acute-phase protein serum amyloid A-1, whereas expression of hepcidin-1 and -2, LPS-binding protein, ceruloplasmin, plasminogen activator inhibitor-1 and thrombospondin-1 was IL-6- independent. In conclusion, in the absence of overt metabolic alterations, IL-6 modulates leukocytosis,thrombopoiesis induction of SAA-1, but not other acute-phase proteins in obese mice.
Issue Date: 2011-12
Publisher: Elsevier
Citation Info: Pini, M., Rhodes, D. H., & Fantuzzi, G. 2011. Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice. Cytokine, 56(3):708-16. doi.org/10.1016/j.cyto.2011.09.015
Type: Article
Description: NOTICE: this is the author’s version of a work that was accepted for publication in Cytokine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cytokine, Vol 56, Issue 3, (December 2011). doi.org/10.1016/j.cyto.2011.09.015
URI: http://hdl.handle.net/10027/8605
ISSN: 1043-4666
Date Available in INDIGO: 2012-08-21
 

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