Nyambuya Tawanda Maurice, Dludla Phiwayinkosi Vusi, Nkambule Bongani Brian
School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban 4013, South Africa.
Department of Health Sciences, Faculty of Health and Applied Sciences, Namibia University of Science and Technology, Windhoek 10005, Namibia.
Biology (Basel). 2021 Mar 12;10(3):217. doi: 10.3390/biology10030217.
This study was conducted to assess the expression of Fas (CD95) and programmed cell death-1 (PD-1) on circulating T-cells in obesity using a diet-induced obesity mouse model. Furthermore, we aimed to determine if there are any associations between metabolic disorders and the expression of T-cell regulatory markers. A total of 12 male C57BL/6 mice were randomized into either a high-fat diet (HFD) or low-fat diet (LFD) group for 8 weeks ( = 6/group). Changes in body weights were monitored on a weekly basis. The lipid, glucose, and hematological profiles, as well as Fas and PD1 expression on the T-cell immunophenotype, were measured after 8 weeks of feeding. The HFD-fed group had a higher percentage weight gain (29.17%) in comparison with the LFD-fed group (21.74%) after the 8-week period. In addition, the HFD group had increased fasting glucose and glucose excursion following a 2-h postprandial period. The levels of total cholesterol were elevated in the HFD group when compared with the LFD group ( < 0.05). Notably, the absolute white cell count ( = 0.0096), neutrophil count ( = 0.0022, lymphocytes ( = 0.0155), and monocyte count ( = 0.0015) were elevated in the HFD group when compared with the LFD-fed group. However, the platelets (0.0680), red cell counts (0.3575), and their indices ( > 0.05) were comparable between the two groups. Interestingly, HFD feeding was associated with elevated expression of Fas on T-cells ( < 0.0001), which positively correlated with body weights ( = 0.93, = 0.0333). No associations were found between Fas expression and dyslipidemia or fasting blood glucose levels ( > 0.05). The multivariant regression analysis showed that the association between the levels of Fas on T-cells and body weights (coefficient: -1.00, -value: 19.27, = 0.0330) was independent of fasting blood glucose, total cholesterol, and lymphocyte count. Lastly, the expression of PD-1 on T-cells was comparable between the two diet groups ( = 0.1822). In all, immune activation, dyslipidemia, and poor glucose control in the early stages of obesity may drive the pathogenesis of metabolic T-cell disorders. Importantly, T-cell dysfunction in obesity is partially mediated by an upregulation of Fas which is independent of dyslipidemia and hyperglycemia.
本研究旨在利用饮食诱导的肥胖小鼠模型，评估肥胖状态下循环T细胞上Fas（CD95）和程序性细胞死亡蛋白1（PD-1）的表达。此外，我们旨在确定代谢紊乱与T细胞调节标志物表达之间是否存在任何关联。总共12只雄性C57BL/6小鼠被随机分为高脂饮食（HFD）组或低脂饮食（LFD）组，为期8周（每组n = 6）。每周监测体重变化。喂养8周后，测量血脂、血糖和血液学指标，以及T细胞免疫表型上Fas和PD1的表达。8周后，高脂饮食喂养组的体重增加百分比（29.17%）高于低脂饮食喂养组（21.74%）。此外，高脂饮食组在餐后2小时的空腹血糖和血糖波动增加。与低脂饮食组相比，高脂饮食组的总胆固醇水平升高（P < 0.05）。值得注意的是，与低脂饮食喂养组相比，高脂饮食组的绝对白细胞计数（P = 0.0096）、中性粒细胞计数（P = 0.0022）、淋巴细胞（P = 0.0155）和单核细胞计数（P = 0.0015）均升高。然而，两组之间的血小板（P = 0.0680）、红细胞计数（P = 0.3575）及其指标（P > 0.05）相当。有趣的是，高脂饮食喂养与T细胞上Fas表达升高有关（P < 0.0001），这与体重呈正相关（r = 0.93，P = 0.0333）。未发现Fas表达与血脂异常或空腹血糖水平之间存在关联（P > 0.05）。多变量回归分析表明，T细胞上Fas水平与体重之间的关联（系数：-1.00；P值：19.27；P = 0.0330）独立于空腹血糖、总胆固醇和淋巴细胞计数。最后，两个饮食组之间T细胞上PD-1的表达相当（P = 0.1822）。总之，肥胖早期的免疫激活、血脂异常和血糖控制不佳可能驱动代谢性T细胞疾病的发病机制。重要的是，肥胖中的T细胞功能障碍部分由Fas上调介导，这独立于血脂异常和高血糖。
