Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Henan Xinxiang 453003, China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, Henan 453003, China; School of Medicine, Xinxiang University, Henan Xinxiang 453003, China.
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Henan Xinxiang 453003, China; Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, Henan 453003, China.
Int Immunopharmacol. 2021 Dec;101(Pt A):108209. doi: 10.1016/j.intimp.2021.108209. Epub 2021 Oct 5.
Obesity is a syndrome that attributes to many factors such as genetics, diet, lifestyle and environment, which includes an imbalance of immune regulation. IL-33, as a new member of the IL-1 family, is classically associated with type 2 immune responses. Here, IL-33 was investigated for its ability to optimize lipid aggregation and ameliorate the inflammatory response in obesity. In vitro experimental results showed that, compared with the induction group, the treatment with 30 ng/mL IL-33 displayed a reduction in the number of lipid droplets. The expression levels of AceCS1 and PPARγ also decreased in the 30 ng/mL IL-33 group compared to the induction group. For confirmation in vivo, three groups of C57BL/6 mice were treated for 14 weeks: mice in control were fed with a normal diet; mice in the HFD and IL-33 groups were fed with a high-fat diet (HFD) and with sterile PBS or recombinant IL-33, respectively. Liver, muscle, spleen and four types of adipose tissue, as well as serum, were collected for further testing. Our data demonstrated that after 4-week treatment with recombinant IL-33, metabolic parameters in mice were improved significantly (visceral fat weight, glucose and insulin tolerance, liver steatosis, expression of lipid synthesis index and inflammatory response). Moreover, IL-33 treatment regulated the original distribution of IL-33 among different tissues. Hence, IL-33 modulated lipid metabolism and inflammatory response in obesity, which would be a novel therapeutic target for obesity and related metabolic diseases.
肥胖是一种与多种因素有关的综合征，如遗传、饮食、生活方式和环境等，其中包括免疫调节失衡。IL-33 作为 IL-1 家族的新成员，与 2 型免疫反应有关。在这里，研究了 IL-33 优化脂质聚集和改善肥胖炎症反应的能力。体外实验结果表明，与诱导组相比，30ng/mL 的 IL-33 处理可减少脂滴数量。与诱导组相比，30ng/mL 的 IL-33 组 AceCS1 和 PPARγ 的表达水平也降低了。为了在体内进行验证，用三种 C57BL/6 小鼠进行了 14 周的治疗：对照组小鼠用正常饮食喂养；HFD 和 IL-33 组小鼠用高脂肪饮食（HFD）和无菌 PBS 或重组 IL-33 喂养。收集肝脏、肌肉、脾脏和四种脂肪组织以及血清进行进一步检测。我们的数据表明，用重组 IL-33 治疗 4 周后，小鼠的代谢参数显著改善（内脏脂肪重量、葡萄糖和胰岛素耐量、肝脂肪变性、脂质合成指数和炎症反应的表达）。此外，IL-33 治疗调节了 IL-33 在不同组织中的原始分布。因此，IL-33 调节肥胖中的脂质代谢和炎症反应，这将是肥胖和相关代谢性疾病的一个新的治疗靶点。
