高脂饮食诱导的肥胖小鼠中缺氧对胰岛素抵抗及脂肪组织巨噬细胞浸润的影响  

Effects of hypoxia on insulin resistance and macrophage infiltration in adipose tissues of diet-induced obesity mice

作　　者：张莉亚[1] 苗青[1] 李益明[1] 叶红英[1] 

机构地区：[1]复旦大学附属华山医院内分泌科,上海200040

出　　处：《复旦学报（医学版）》2015年第4期467-472,共6页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金(30600300)~~

摘　　要：目的研究缺氧在高脂饮食诱导的肥胖(diet-induced obesity,DIO)小鼠模型中对胰岛素抵抗及脂肪组织巨噬细胞浸润的影响。方法建立DIO小鼠模型,动态观察高脂饮食(high-fat diet,HFD)喂养小鼠4、8、12周时的体质量、白色脂肪(white adipose tissue,WAT)量及其与体质量的比值、空腹血糖、空腹胰岛素、糖耐量和胰岛素抵抗、脂肪组织中F4/80标记的巨噬细胞浸润,采用hypoxyprobeTM-1试剂盒(哌莫硝唑标记法)评价DIO小鼠的脂肪组织是否存在缺氧及其出现时间,分析缺氧与上述指标异常出现的时间先后,探讨缺氧在HFD致胰岛素抵抗、脂肪组织巨噬细胞浸润中的作用。结果 DIO小鼠4周时即出现糖耐量异常,8周时出现胰岛素抵抗;WAT存在局部缺氧,与巨噬细胞浸润增加同步出现在HFD后12周时间点,迟于糖耐量异常和胰岛素抵抗的出现。结论缺氧可能不是DIO时糖代谢异常和胰岛素抵抗的启动因素。Objective To study the effects of hypoxia on insulin resistance and macrophage infiltration in diet-induced obesity （DIO） mice. Methods The model of DIO mice was established. The time course of body weight,white adipose tissue （WAT） wet weight and its ratio to body weight, FBG,FINS,ipGTT, HOMR-IR, macrophage infiltration into adipose tissue stained with anti-F4/80 in high-fat diet （HFD） fed mice after 4, 8 and 12 wk were investigated. The hypoxyprobeTM-1 kit （pimonidazole staining） was applied to find out the existence of hypoxia in adipose tissue,and then its potential role in insulin resistance and macrophage infiltration into obese adipose tissue was investigated. Results Impaired ipGTT occurred at 4 wk,insulin resistance occurred at 8 wk; The existence of local hypoxia in WAT was detected at 12 wk and was accompanied with macrophage infiltration,occurring later than impaired ipGTT and insulin resistance. Conclusions Hypoxia may not be the trigger factor of HFD induced impaired glucose metabolism and insulin resistance.

关 键 词：高脂饮食 高脂饮食诱导肥胖 脂肪组织 炎症 缺氧 巨噬细胞 小鼠 

分 类 号：R58[医药卫生—内分泌]