Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice.
Blocking high-fat diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice.
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DOI：
10.1038/ijo.2015.52
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Liu D
中科院分区：
文献类型：
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作者：
Darkhal P;Gao M;Ma Y;Liu D
本研究的目的是评价抗炎细胞因子IL-13在阻断高脂饮食诱导的肥胖及肥胖相关的胰岛素抵抗和肝脏脂肪变性中的作用。C57BL/6小鼠被喂以高脂饲料，并接受携带小鼠IL-13或GFP(对照)基因的质粒的流体动力传递。连续监测小鼠IL-13血蛋白水平、摄食量和体重，观察8周。实验结束时，测定试验组和对照组动物的脂肪和瘦肉量。测定血糖、胰岛素和血脂浓度，用实时荧光定量聚合酶链式反应检测脂肪组织中巨噬细胞标志基因和能量代谢相关基因的mRNA水平。进行糖耐量和胰岛素敏感性试验，以确定葡萄糖稳态。采用组织化学和脂质分析方法检测肝脏脂质蓄积。IL-13的血药浓度在基因导入后1周为20 ng/ml，并随时间延长而下降。IL-13的过表达可以在不影响食物摄入量的情况下阻止高脂饮食导致的体重增加。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，肝脏中的脂肪堆积较少。IL-13的过表达阻断了脂肪组织中巨噬细胞的浸润，抑制了高脂饮食诱导的炎性F4/80、CD68和Mcp1的表达，并抑制了与能量消耗有关的Ucp1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、肥胖相关的胰岛素抵抗和脂肪肝的有效策略。
The objective of this study is to assess the activity of anti-inflammatory cytokine IL-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 one 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 expression of Ucp1 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.