Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice
Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice
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DOI：
10.1016/j.cyto.2011.09.015
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发表时间：
2011-12-01
期刊：
影响因子：
3.8
通讯作者：
Fantuzzi, Giamila
中科院分区：
文献类型：
--
作者：
Pini, Maria;Rhodes, Davina H.;Fantuzzi, Giamila
肥胖与慢性炎症和IL-6水平升高有关。IL-6在诱导急性期蛋白质和调节血液学反应中的作用已在炎症和衰老模型中得到证实，但在肥胖症中没有。我们假设，IL-6是必要的，以调节急性相反应和血液学变化与饮食诱导的肥胖（DIO）小鼠。与喂食普通饲料的小鼠相比，对C57 BL 6 WT雄性小鼠喂食60% kcal/脂肪饲料13周诱导内脏脂肪组织（VAT）而非肝脏中IL-6表达显著增加。与瘦小鼠相比，DIO小鼠腹腔灌洗液中IL-6水平显著升高，而血浆中IL-6水平无显著升高。与喂食普通饲料的WT和KO小鼠相比，DIO WT和IL-6 KO小鼠的肥胖、肝肿大、高瘦素血症、VAT炎症和胰岛素抵抗程度相当。与瘦型组相比，在DIO WT但非DIO KO小鼠中观察到显著的白细胞增多。与其他组相比，DIO KO小鼠的血小板计数显著降低，而血小板大小、循环网织血小板百分比和骨髓巨核细胞数量无变化。血小板生成素的肝脏表达在各组中相当，与瘦小鼠相比，010 WT和KO小鼠具有降低的VAT表达。与其他组相比，瘦KO小鼠的血小板生成素血浆水平显著升高，而肝脏相关的血小板生成素水平在各组中相当。IL-6缺乏导致急性时相蛋白血清淀粉样蛋白A-1的肝脏诱导减弱，而hepcidin-1和-2，LPS结合蛋白，血浆铜蓝蛋白，纤溶酶原激活物抑制剂-1和血小板反应蛋白-1的表达不依赖于IL-6。总之，在没有明显的代谢改变的情况下，IL-6调节白细胞增多、血小板生成和SAA-1的诱导，但不调节肥胖小鼠中的其他急性期蛋白。(C)2011爱思唯尔有限公司保留所有权利。
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 hematological 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 010 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 and induction of SAA-1, but not other acute-phase proteins in obese mice. (C) 2011 Elsevier Ltd. All rights reserved.