OBJECTIVE To evaluate T-helper cytokine responses in a short-term high fat diet (HFD) induced impaired glucose metabolism. To further evaluate the modulation of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines using short-term low-dose aspirin in combination with metformin. DESIGN Two experiments were carried out in this study in order to evaluate the T-helper cytokine profiles in a state of impaired glucose metabolism. A total of 28 six-week-old male C57BL/6 mice were used in this study. In the first experiment, mice were fed either a high fat diet or low fat diet for a duration of 10 weeks. We then determined the Th1, Th2 and T-helper 17 (Th17) cytokine profiles. In the second experiment, we evaluated whether the short term 6-week treatment with low-dose aspirin in combination with metformin modulates T-helper cytokine profiles of the HFD-fed mice. MEASUREMENTS In the first experiment, we measured the body weights, blood glucose levels, insulin levels, lipid profiles and haematological parameters. We further performed oral glucose tolerance testing following an 8-hour fast and serum Th1, Th2 and Th17 cytokine levels were also determined following short-term 8-week diet-feeding and 6-week low-dose aspirin and combined metformin with low-dose aspirin treatment. RESULTS High fat diet-feeding caused a marked increase in circulating peripheral blood lymphocytes, which was attenuated by short-term low-dose aspirin treatment. Moreover, the HFD feeding resulted in 2-fold increase in total cholesterol and a 4-fold increase in low-density lipoprotein cholesterol when compared to the low-fat diet-fed group (p < 0.05). In the high fat diet group, impaired glucose metabolism was associated with skewed Th2 responses without alterations in the Th1 and Th17 cytokine profiles. Interestingly the short-term treatment with low-dose aspirin showed no effect on the selected T-helper 1 cytokine IFN-Ƴ (P > 0.05). While the combination of low-dose aspirin with metformin considerably reduced the levels of serum IFN-Ƴ (P < 0.05). Furthermore low-dose aspirin treatment showed the modest attenuation of the selected Th2 cytokines, IL-10 and IL-13 when compared to low-dose aspirin with metformin (P < 0.01). CONCLUSION The early immunological and metabolic changes that occur in a state impaired glucose tolerance are accompanied by the increased production of Th2 cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th2 cell responses.

中文翻译：

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高脂肪饮食喂养的 C57BL/6 小鼠中升高的 T-helper 2 细胞因子水平通过短期 6 周治疗与低剂量阿司匹林和二甲双胍的组合减弱

目的 评估短期高脂饮食 (HFD) 诱导的葡萄糖代谢受损中的 T 辅助细胞因子反应。为了进一步评估使用短期低剂量阿司匹林与二甲双胍组合对 T-helper 1 (Th1) 和 T-helper 2 (Th2) 细胞因子的调节。设计 本研究中进行了两个实验，以评估葡萄糖代谢受损状态下的 T 辅助细胞因子谱。本研究共使用 28 只 6 周龄雄性 C57BL/6 小鼠。在第一个实验中，小鼠被喂食高脂肪饮食或低脂肪饮食，持续 10 周。然后我们确定了 Th1、Th2 和 T-helper 17 (Th17) 细胞因子谱。在第二个实验中，我们评估了低剂量阿司匹林联合二甲双胍的短期 6 周治疗是否会调节 HFD 喂养小鼠的 T 辅助细胞因子谱。测量 在第一个实验中，我们测量了体重、血糖水平、胰岛素水平、血脂和血液学参数。我们在禁食 8 小时后进一步进行了口服葡萄糖耐量测试，并且在短期 8 周饮食喂养和 6 周低剂量阿司匹林以及联合二甲双胍和低剂量二甲双胍后也测定了血清 Th1、Th2 和 Th17 细胞因子水平。阿司匹林治疗。结果 高脂肪饮食导致循环外周血淋巴细胞显着增加，短期低剂量阿司匹林治疗减弱了这种增加。而且，与低脂饮食喂养组相比，HFD 喂养导致总胆固醇增加 2 倍，低密度脂蛋白胆固醇增加 4 倍（p < 0.05）。在高脂肪饮食组中，葡萄糖代谢受损与 Th2 反应偏态有关，而 Th1 和 Th17 细胞因子谱没有改变。有趣的是，低剂量阿司匹林的短期治疗对选定的 T-helper 1 细胞因子 IFN-Ƴ 没有影响（P > 0.05）。而低剂量阿司匹林与二甲双胍的组合显着降低了血清 IFN-Ƴ 的水平（P < 0.05）。此外，与低剂量阿司匹林和二甲双胍相比，低剂量阿司匹林治疗显示出所选 Th2 细胞因子、IL-10 和 IL-13 的适度衰减（P < 0.01）。结论 在糖耐量受损状态下发生的早期免疫和代谢变化伴随着 Th2 细胞细胞因子的增加。使用低剂量阿司匹林联合二甲双胍的短期治疗可能在预防与 Th2 细胞反应失调相关的并发症方面提供治疗益处。