Department of Inflammation, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
PPAR Res. 2010;2010:970164. doi: 10.1155/2010/970164. Epub 2010 Apr 22.
The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/ 0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6.
在高脂肪和高胆固醇饮食诱导的肥胖（DIO）小鼠模型中，评估了与肥胖相关的代谢和炎症参数的动力学。研究表明，过氧化物酶体增殖物激活受体γ激动剂罗格列酮可调节细胞浸润和介质的产生。将 C57BL/6 小鼠维持在 45%脂肪/0.12%胆固醇（HF/CH）或 Chow 饮食中 3、6、16 或 27 周。流式细胞术用于监测外周血单核细胞和脂肪组织巨噬细胞（ATM）。使用基因表达和蛋白质分析方法来评估总附睾脂肪（EF）、基质血管部分（SVF）和分选的 SVF 细胞中介质的产生。为了研究治疗干预，将小鼠用 HF/CH 饮食喂养 12 周，然后用含有罗格列酮（5mg/kg）的饮食再喂养 6 周。HF/CH 饮食与肥胖和剧烈的促炎状态相关。用罗格列酮进行治疗干预可减轻 HF/CH 引起的炎症。此外，还发现了一个表达促炎介质 CCL2 和 IL-6 水平最高的新群体。
