Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390, USA.
J Lipid Res. 2012 Jul;53(7):1254-67. doi: 10.1194/jlr.M021725. Epub 2012 Apr 13.
Subclinical inflammation is frequently associated with obesity. Here, we aim to better define the acute inflammatory response during fasting. To do so, we analyzed representatives of immune-related proteins in circulation and in tissues as potential markers for adipose tissue inflammation and modulation of the immune system. Lipopolysaccharide treatment or high-fat diet led to an increase in circulating serum amyloid (SAA) and α1-acid glycoprotein (AGP), whereas adipsin levels were reduced. Mouse models that are protected against diet-induced challenges, such as adiponectin-overexpressing animals or mice treated with PPARγ agonists, displayed lower SAA levels and higher adip-sin levels. An oral lipid gavage, as well as prolonged fasting, increased circulating SAA concurrent with the elevation of free FA levels. Moreover, prolonged fasting was associated with an increased number of Mac2-positive crown-like structures, an increased capillary permeability, and an increase in several M2-type macrophage markers in adipose tissue. This fasting-induced increase in SAA and M2-type macrophage markers was impaired in metabolically challenged animals. These data suggest that metabolic inflexibility is associated with a lack of "immunological fitness."
亚临床炎症常与肥胖有关。在这里，我们旨在更好地定义禁食期间的急性炎症反应。为此，我们分析了循环中和组织中与免疫相关的蛋白质代表，作为脂肪组织炎症和免疫系统调节的潜在标志物。脂多糖处理或高脂肪饮食导致循环血清淀粉样蛋白 (SAA) 和α1-酸性糖蛋白 (AGP) 增加，而脂联素水平降低。例如，脂联素过表达动物或用 PPARγ 激动剂治疗的小鼠等对饮食诱导的挑战具有保护作用的小鼠模型，其 SAA 水平较低，脂联素水平较高。口服脂质灌胃和长时间禁食会增加循环 SAA，同时游离 FA 水平升高。此外，长时间禁食与脂肪组织中 Mac2 阳性冠状结构数量增加、毛细血管通透性增加以及几种 M2 型巨噬细胞标志物增加有关。在代谢受到挑战的动物中，这种禁食引起的 SAA 和 M2 型巨噬细胞标志物增加受到损害。这些数据表明，代谢灵活性与缺乏“免疫适应性”有关。
