Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin
Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin
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DOI：
10.1016/j.cyto.2020.154999
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发表时间：
2020-04-01
期刊：
影响因子：
3.8
通讯作者：
Nkambule, Bongani B.
中科院分区：
文献类型：
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作者：
Mahlangu, Thabsile J.;Dludla, Phiwayinkosi, V;Nkambule, Bongani B.
目的：探讨短期高脂饮食（HFD）诱导的糖代谢异常对辅助性T细胞因子的影响。为了进一步评估调制辅助性T细胞1（Th-1）和辅助性T细胞2（Th-2）细胞因子使用短期低剂量阿司匹林与metformin.Design组合：两个实验进行了这项研究，以评估辅助性T细胞因子的配置文件在糖代谢受损的状态。在本研究中使用总共28只六周龄雄性C57 BL/6小鼠。在第一个实验中，给小鼠喂食高脂肪饮食或低脂肪饮食，持续10周。然后，我们确定了Th-1，Th-2和辅助性T细胞17（Th-17）细胞因子谱。在第二个实验中，我们评估是否短期6周治疗低剂量阿司匹林与二甲双胍组合调制辅助性T细胞因子的HFD喂养mice.Measurements：在第一个实验中，我们测量了体重，血糖水平，胰岛素水平，血脂谱和血液学参数。我们在禁食8小时后进一步进行口服葡萄糖耐量试验，并在短期8周饮食喂养和6周低剂量阿司匹林以及二甲双胍与低剂量阿司匹林联合治疗后测定血清Th-1、Th-2和Th-17细胞因子水平。高脂饮食喂养引起循环外周血淋巴细胞显着增加，这是由短期低剂量阿司匹林治疗减弱。此外，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）。在高脂饮食组中，糖代谢受损与Th-1和Th-17细胞因子谱无改变的偏斜反应相关。有趣的是，低剂量阿司匹林短期治疗对选定的T-helper 1细胞因子IFN-γ无影响（P > 0.05）。小剂量阿司匹林联合二甲双胍治疗可显著降低血清IFN-γ水平（P < 0.05）。结论：糖耐量异常患者早期免疫和代谢改变伴随Th-2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Th-2细胞反应失调相关的并发症方面提供治疗益处。
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 (Th-1) and T-helper 2 (Th-2) cytokines using shortterm 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 Th-1, Th-2 and T-helper 17 (Th-17) 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 Th-1, Th-2 and Th-17 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 The responses without alterations in the Th-1 and Th-17 cytokine profiles. Interestingly the short-term treatment with low-dose aspirin showed no effect on the selected T-helper 1 cytokine IFN-Upsilon(P > 0.05). While the combination of low-dose aspirin with metformin considerably reduced the levels of serum IFN-Upsilon (P < 0.05). Furthermore low-dose aspirin treatment showed the modest attenuation of the selected The 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 Th-2 cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th-2 cell responses.