University of KwaZulu-Natal (UKZN), University Road, Westville, Private Bag X54001, Durban 4000, South Africa.
Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg 7505, South Africa; Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona 60131, Italy.
Cytokine. 2020 Apr;128:154999. doi: 10.1016/j.cyto.2020.154999. Epub 2020 Jan 31.
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) and T-helper 2 (Th) cytokines using short-term low-dose aspirin in combination with metformin.
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, Th and T-helper 17 (Th) 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.
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, Th and Th 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.
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 Th responses without alterations in the Th and Th 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 Th cytokines, IL-10 and IL-13 when compared to low-dose aspirin with metformin (P < 0.01).
The early immunological and metabolic changes that occur in a state impaired glucose tolerance are accompanied by the increased production of Th cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th cell responses.
评估短期高脂饮食（HFD）引起的葡萄糖代谢受损中的辅助性 T 细胞细胞因子反应。进一步评估短期低剂量阿司匹林联合二甲双胍对辅助性 T 细胞 1（Th）和辅助性 T 细胞 2（Th）细胞因子的调节作用。
本研究进行了两项实验，以评估葡萄糖代谢受损状态下的辅助性 T 细胞细胞因子谱。总共使用了 28 只 6 周龄雄性 C57BL/6 小鼠进行这项研究。在第一项实验中，小鼠接受高脂饮食或低脂饮食 10 周。然后我们确定了 Th、Th 和 Th17（Th）细胞因子谱。在第二项实验中，我们评估了短期 6 周低剂量阿司匹林联合二甲双胍治疗是否调节了 HFD 喂养小鼠的辅助性 T 细胞细胞因子谱。
在第一项实验中，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。在 8 小时禁食后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低剂量阿司匹林联合二甲双胍治疗后，还测定了血清 Th、Th 和 Th 细胞因子水平。
高脂饮食喂养导致循环外周血淋巴细胞明显增加，短期低剂量阿司匹林治疗可减轻这种增加。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，葡萄糖代谢受损与 Th 反应偏斜有关，而 Th 和 Th 细胞因子谱没有改变。有趣的是，短期低剂量阿司匹林治疗对所选 Th1 细胞因子 IFN-γ（P>0.05）没有影响。而低剂量阿司匹林联合二甲双胍则显著降低了血清 IFN-γ 水平（P<0.05）。此外，与低剂量阿司匹林联合二甲双胍相比，低剂量阿司匹林治疗对所选 Th 细胞因子 IL-10 和 IL-13 的抑制作用较小（P<0.01）。
在葡萄糖耐量受损状态下发生的早期免疫和代谢变化伴随着 Th 细胞细胞因子产生的增加。短期使用低剂量阿司匹林联合二甲双胍可能在预防与 Th 细胞反应失调相关的并发症方面提供治疗益处。
