摘要
背景:实验室前期研究发现青年脂肪干细胞移植到老年小鼠体内会有减重效果,并且能改善老年小鼠体内炎症状态,推测类胰岛素生长因子1可能对于衰老和肥胖具有重要作用。目的:探究类胰岛素生长因子1对自然衰老小鼠的抗肥胖作用。方法:①生物信息学分析:对GEO数据库中肥胖患者的脂肪组织测序,并对青年小鼠脂肪干细胞和老年小鼠脂肪干细胞进行转录组学测序,分析类胰岛素生长因子1表达情况。②动物实验验证:2月龄雄性C57BL/6J小鼠(青年小鼠)6只,20月龄雄性C57BL/6J小鼠(老年小鼠)12只。采用ELISA和qRT-PCR检测青年小鼠和老年小鼠的腹部脂肪组织和血清类胰岛素生长因子1的表达情况。将老年小鼠12只随机分为2组:实验组连续4周注射类胰岛素生长因子1蛋白(50μg/kg),对照组注射同等剂量的PBS。定期监测实验组和对照组小鼠体质量变化,实验结束时测量小鼠葡萄糖耐受,ELISA检测小鼠血清炎症因子、腹部脂肪组织炎症因子,苏木精-伊红染色观察肝、肾及腹部脂肪组织病理变化,qRT-PCR检测腹部脂肪组织炎症因子、PI3K-AKT信号通路mRNA的表达水平。结果与结论:①肥胖患者脂肪组织低表达类胰岛素生长因子1,并在接受减肥手术后类胰岛素生长因子1表达上升;②老年脂肪干细胞低表达类胰岛素生长因子1;③老年小鼠腹部脂肪组织和血清均低表达类胰岛素生长因子1;④注射类胰岛素生长因子1蛋白能显著降低老年小鼠的体质量并改善胰岛素抵抗;⑤老年小鼠肝脏病理切片发现有脂肪堆积情况,注射类胰岛素生长因子1蛋白后,脂肪堆积情况显著改善,并且显著降低了脂肪组织的脂滴大小;⑥注射类胰岛素生长因子1能显著降低老年小鼠血清肿瘤坏死因子α、白细胞介素1β、白细胞介素6的表达水平,显著增加脂肪组织PI3K-AKT信号通路的表达;⑦结论:外源性类胰岛素生长因子1能降低老年小鼠体质量、减小脂肪组织脂滴大小及改善肝脏脂肪堆积情况,改善老年小鼠的炎症状态,可能是通过激活PI3K-AKT信号通路改善老年小鼠的炎症状态,从而改善自然衰老小鼠的肥胖。
BACKGROUND:In our previous experiments,it was found that transplantation of young adipose stem cells into aged mice would have weight loss effect and improve the inflammatory state in aged mice.Therefore,we speculate that insulin-like growth factor 1 may play an important role in aging and obesity.OBJECTIVE:To explore the anti-obesity effect of insulin-like growth factor 1 in naturally aging mice.METHODS:(1)Bioinformatics analysis:Sequencing of adipose tissue from obese patients in the GEO database and transcriptomic sequencing of young mouse adipose stem cells and old adipose stem cells were conducted to analyze insulin-like growth factor 1 expression.(2)Animal experiment verification:Six young C57BL/6J mice and twelve aged C57BL/6J mice(20 months old)were selected.Abdominal adipose tissue and serum insulin-like growth factor 1 expression in young and aged mice were examined by ELISA and qRT-PCR.All the 12 aged mice were randomly divided into two groups with 6 mice in each group:the experimental group was given insulin-like growth factor 1(50μg/kg)for 4 continuous weeks,while the control group was given the same amount of phosphate buffer saline.The body mass changes of mice were monitored regularly,glucose tolerance was measured at the end of the experiment,and serum inflammatory factors and inflammatory factors in abdominal white adipose tissue of mice were detected by ELISA.Hematoxylin-eosin staining was used to observe pathological changes in the mouse liver,kidney and abdominal white adipose tissue.The mRNA expression levels of inflammatory factors and PI3K-Akt signaling pathway in abdominal white adipose tissue of mice were detected by qRT-PCR.RESULTS AND CONCLUSION:Obese patients showed lowly expressed insulin-like growth factor 1 in adipose tissue,but the expression of insulin-like growth factor 1 increased after weight loss surgery.Insulin-like growth factor 1 expressed lowly in aged adipose stem cells.Insulin-like growth factor 1 also showed a low expression in adipose tissue and serum of aged mice.Injection of insulin-like growth factor 1 protein could significantly reduce the body mass of aged mice and improve insulin resistance.Pathological sections of the liver of aged mice revealed fat accumulation.After injection of insulin-like growth factor 1 protein,fat accumulation was significantly improved and the size of fat droplets in adipose tissue was significantly reduced.Insulin-like growth factor 1 injection significantly reduced the expression levels of serum tumor necrosis factorα,interleukin 1β,and interleukin 6 in aged mice,and significantly increased the expression of PI3K-AKT signaling pathway in adipose tissue of aged mice.To conclude,exogenous insulin-like growth factor 1 can reduce body mass,reduce fat droplet size in adipose tissue,and improve liver fat accumulation in aged mice,thereby improving their inflammatory status.Exogenous insulin-like growth factor 1 may activate the PI3K-AKT signaling pathway to improve the inflammatory symptoms in aged mice,thereby improving obesity in naturally aging mice.
作者
朱鹏
李瑛玉
卢小倩
吴琼
Zhu Peng;Li Yingyu;Lu Xiaoqian;Wu Qiong(Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology(Guangxi Normal University),Guilin 541004,Guangxi Zhuang Autonomous Region,China;College of Life Sciences,Guangxi Normal University,Guilin 541006,Guangxi Zhuang Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2025年第12期2536-2543,共8页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(32160170),项目负责人:吴琼。
