用~1H-MRS评价利拉鲁肽对肥胖小鼠脂质代谢影响的研究

Effects of Liraglutide on Lipid Metabolism in Obese Mice Using ~1H-MRS

目的运用氢质子磁共振波谱(proton magnetic resonance spectroscopy,^1H-MRS)评价利拉鲁肽(liraglutide)对肥胖小鼠模型体内不同部位、不同性质脂肪代谢的影响。方法将32只6周龄清洁级C57BL6雄性小鼠随机分为4组,每组8只,其中一组给予正常饮食,另外3组给予高脂饮食以建立肥胖小鼠模型。8周后,与正常饮食组比较,高脂饮食组体质量平均增长超过30%,表明肥胖小鼠造模成功。将成功造模后的高脂饮食组随机分为利拉鲁肽(glucagon-like peptide-1,GLP-1)组、隔日禁食(altenative day fasting,ADF)组和高脂对照(high-fat diet,HFD)组,GLP-1组和HFD组分别继续给予高脂饮食,ADF组与正常对照(control)组给予普通饲料喂养。GLP-1组每日皮下注射利拉鲁肽0.4mg/(kg·d),ADF组为每隔24h给予正常饲料,期间自由饮水。干预16周末,取活体小鼠,在9.4T MicroMR成像设备上通过氢质子磁共振波谱(proton magnetic resonance spectroscopy,^1H-MRS)技术检测各组小鼠肩胛间区棕色脂肪、肝脏及腹股沟区白色脂肪的甘油三酯(triglyceride,TG)含量。结果干预前各组小鼠体质量比较差异无统计学意义,随喂养时间的延长,各组小鼠平均体质量均呈明显升高的趋势(P<0.05)。干预16周末,GLP-1组小鼠平均体质量明显低于HFD(P=0.009),而高于正常对照组(P=0.011),差异均有统计学意义(P<0.05)。4组小鼠肩胛部棕色脂肪TG平均含量比较未发现各组之间差异有统计学意义。肝脏TG平均含量比较发现,仅GLP-1和HFD之间差异有统计学意义(P=0.045)。腹股沟白脂肪TG平均含量比较发现,与GLP-1小鼠比较,正常对照组小鼠腹股沟白脂肪TG平均含量明显降低(P=0.002),HFD组小鼠腹股沟白脂肪TG平均含量明显升高(P=0.015)。结论利拉鲁肽可显著降低肥胖小鼠体质量,改善肥胖小鼠脂质代谢,尤其在改善肝脏脂质代谢方面表现出格外优势,表明利拉鲁肽在通过减轻体质量所致整体代谢参数的改善的同时,还有不依赖于体改善影响脂质代谢的其他途径。

Objective To observe the effect of lipid metabolism of liralgutide in different parts of obese mice which evaluated by proton magnetic resonance spectroscopy(^1H-MRS).Methods 32 clean grade C57BL6 male mice aged 6 weeks were randomly divided into high-fat diet group(n=24)and normal controlgroup(n=8).After 8 weeks,the average body weight of the high-fat diet group increased more than 30%than that of the control group,which indicated that the model of high fat was successful.The high-fat diet group was randomly divided into three groups:the GLP-1 group,the ADF group and the HFD group.GLP-1 group and HFD group were fed with high-fat diet respectively,the ADF and the normal control group were fed with normal diet.The GLP-1 group was given daily subcutaneous injection of liraglutide 0.4mg/(kg·d).The ADF group was given normal diet every 24 hours,during which free drinking water was given.At the end of 16 weeks of intervention,the relative fat content in the interscapular area,the white fat in liver and inguinal area of mice was measured by ^1H-MRS.Results Before intervention,there was no significant difference in the weight of each group.With the prolongation of feeding time,the average body weight of each group was obviously increased(P<0.05).At the end of 16 weeks,the average body weight of GLP-1 group was significantly lower than that of HFD(P=0.009),but higher than that of Control(P=0.011),and the difference was statistically significant(P<0.05).As for comparison of TG content in different parts of four groups after intervention under ^1H-MRS,there was no significant difference in the average TG content of brown fat in scapula between the four groups.Only the difference between GLP-1 and HFD was statistically significant(P=0.045).Compared with GLP-1 mice,the average content of TG in inguinal white fat in Control group was significantly lower than that in GLP-1 mice(P=0.002).The average TG content of inguinal white fat in HFD group was significantly higher than that in Control group(P=0.015).Conclusion Liraglutide can significantly reduce the body weight of obese mice and improve lipid metabolism in obese mice,especially in improving liver lipid metabolism.While improving the overall metabolic parameters,there are other ways of affecting lipid metabolism independent of body improvement.