Darkhal P, Gao M, Ma Y, Liu D
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, USA.
Int J Obes (Lond). 2015 Aug;39(8):1292-9. doi: 10.1038/ijo.2015.52. Epub 2015 Apr 14.
The objective of this study was to assess the activity of anti-inflammatory cytokine IL-13 (interleukin-13) in blocking high-fat diet-induced obesity and obesity-associated insulin resistance and liver steatosis.
C57BL/6 mice were fed a high-fat diet and received hydrodynamic delivery of plasmids carrying the mouse Il-13 or Gfp (control) gene. IL-13 blood protein levels, food consumption and body weight of mice were continuously monitored for 8 weeks. Fat and lean masses of treated and control animals were determined at the end of the experiment. Serum concentrations of glucose, insulin and lipids were determined, and mRNA levels of macrophage marker genes in adipose tissue and genes involved in energy metabolism were examined using real-time PCR. Glucose tolerance and insulin sensitivity tests were performed to determine glucose homeostasis. Histochemistry and lipid assays were performed to determine the hepatic lipid accumulation.
Blood concentration of IL-13 was 20 ng ml(-1) 1 week after gene delivery and declined with time. Overexpression of Il-13 prevented high-fat diet-induced weight gain without affecting food consumption. Mice that underwent Il-13 gene transfer showed regular body weight and normal serum concentrations of glucose and insulin, and less lipid accumulation in the liver. Overexpression of Il-13 blocked macrophage infiltration in adipose tissue and suppressed high-fat diet-induced expression of inflammatory F4/80, Cd68 and Mcp1, and elevated the expression of Ucp1 (uncoupling protein 1 gene) responsible for energy expenditure.
These results suggest that suppression of diet-induced inflammation by IL-13 is an effective strategy in preventing diet-induced obesity and obesity-associated insulin resistance and fatty liver.
本研究的目的是评估抗炎细胞因子白细胞介素-13（IL-13）在阻断高脂饮食诱导的肥胖、肥胖相关胰岛素抵抗和肝脂肪变性方面的活性。
给C57BL/6小鼠喂食高脂饮食，并通过流体动力学方法递送携带小鼠Il-13或Gfp（对照）基因的质粒。连续8周监测小鼠的IL-13血液蛋白水平、食物摄入量和体重。在实验结束时测定处理组和对照组动物的脂肪和瘦体重。测定血清葡萄糖、胰岛素和脂质浓度，并使用实时PCR检测脂肪组织中巨噬细胞标志物基因以及参与能量代谢的基因的mRNA水平。进行葡萄糖耐量和胰岛素敏感性测试以确定葡萄糖稳态。进行组织化学和脂质测定以确定肝脏脂质积累。
基因递送后1周，IL-13的血液浓度为20 ng ml-1，并随时间下降。Il-13的过表达可防止高脂饮食诱导的体重增加，而不影响食物摄入量。接受Il-13基因转移的小鼠体重正常，血清葡萄糖和胰岛素浓度正常，肝脏中的脂质积累较少。Il-13的过表达可阻止巨噬细胞浸润脂肪组织，并抑制高脂饮食诱导的炎症性F4/80、Cd68和Mcp1的表达，并提高负责能量消耗的解偶联蛋白1（Ucp1）基因的表达。
这些结果表明，IL-13抑制饮食诱导的炎症是预防饮食诱导的肥胖、肥胖相关胰岛素抵抗和脂肪肝的有效策略。
