Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, United States.
Cytokine. 2011 Dec;56(3):708-16. doi: 10.1016/j.cyto.2011.09.015. Epub 2011 Oct 12.
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 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 and induction of SAA-1, but not other acute-phase proteins in obese mice.
肥胖与慢性炎症和 IL-6 水平升高有关。IL-6 在炎症和衰老模型中诱导急性期蛋白和调节血液学反应的作用已得到证实，但在肥胖症中尚未得到证实。我们假设 IL-6 对于调节与饮食诱导肥胖（DIO）相关的急性期反应和血液学变化是必要的。用 60%热量/脂肪饮食喂养 C57BL6 WT 雄性小鼠 13 周，与喂饲标准饮食的小鼠相比，内脏脂肪组织（VAT）中 IL-6 的表达显著增加，但肝脏中没有增加。与瘦鼠相比，DIO 的腹腔灌洗液中 IL-6 水平显著升高，但血浆中没有升高。与喂饲标准饮食的 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。与瘦鼠相比，DIO WT 小鼠出现显著的白细胞增多，但 DIO KO 小鼠没有。与瘦鼠相比，DIO KO 小鼠的血小板计数显著减少，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没有改变。DIO KO 小鼠的肝内血小板生成素表达与其他各组相似，但与瘦鼠相比，DIO WT 和 KO 小鼠的 VAT 表达降低。与其他各组相比，瘦鼠 KO 小鼠的血浆血小板生成素水平显著升高，而各组的肝相关血小板生成素水平相似。IL-6 缺乏导致肝内急性期蛋白血清淀粉样蛋白 A-1 的诱导减弱，而 hepcidin-1 和 -2、LPS 结合蛋白、铜蓝蛋白、纤溶酶原激活物抑制剂-1 和血栓调节蛋白-1 的表达与 IL-6 无关。总之，在没有明显代谢改变的情况下，IL-6 调节肥胖小鼠的白细胞增多、血小板生成和 SAA-1 的诱导，但不调节其他急性期蛋白。
