Yan Linna, Song Kexiu, Gao Mingming, Qu Shen, Liu Dexi
Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA.
Department of Endocrinology, Tongji University School of Medicine, and Shanghai Tenth People's Hospital, Shanghai, People's Republic of China.
Pharm Res. 2016 Feb;33(2):395-403. doi: 10.1007/s11095-015-1797-9. Epub 2015 Sep 28.
To assess the effect of immune modulators, cyclosporin A and fingolimod, on high fat diet-induced obesity and insulin resistance.
C57BL/6 mice were fed a high fat diet and injected intraperitoneally with cyclosporine A, fingolimod, or vehicle twice weekly for 15 weeks. Body weight and food intake were manually measured every other day. Glucose tolerance test, insulin sensitivity, and body composition were examined and compared between the control and the immune modulator treated animals. Tissue samples were collected at the end of the experiment and examined for serum biochemistry, histology, and mRNA levels of marker genes for inflammation, and glucose and lipid metabolism in white and brown adipose tissues and in the liver.
Cyclosporine A and fingolimod suppressed high fat diet-induced weight gain, reduced hepatic fat accumulation, and improved insulin sensitivity. The beneficial effects are associated with altered expression of F4/80, Cd68, Il-6, Tnf-α, and Mcp-1 genes, which are involved in macrophage-related chronic inflammation in adipose and hepatic tissues.
Immune modulation represents an important intervention for obesity and obesity-associated insulin resistance.
评估免疫调节剂环孢素A和芬戈莫德对高脂饮食诱导的肥胖和胰岛素抵抗的影响。
给C57BL/6小鼠喂食高脂饮食，并每周两次腹腔注射环孢素A、芬戈莫德或赋形剂，持续15周。每隔一天手动测量体重和食物摄入量。对对照组和接受免疫调节剂治疗的动物进行葡萄糖耐量试验、胰岛素敏感性和身体成分检测并比较。在实验结束时收集组织样本，检测血清生化指标、组织学以及白色和棕色脂肪组织及肝脏中炎症、葡萄糖和脂质代谢相关标记基因的mRNA水平。
环孢素A和芬戈莫德抑制了高脂饮食诱导的体重增加，减少了肝脏脂肪堆积，并改善了胰岛素敏感性。这些有益作用与F4/80、Cd68、Il-6、Tnf-α和Mcp-1基因表达的改变有关，这些基因参与脂肪和肝脏组织中与巨噬细胞相关的慢性炎症。
免疫调节是肥胖及肥胖相关胰岛素抵抗的重要干预措施。
