利拉鲁肽对高脂诱导肥胖小鼠瘦素、脂肪分布及含量的影响

Effect of liraglutide on leptin and fat content in high fat diet induced obese mice

目的观察利拉鲁肽对高脂诱导的C57BL/6小鼠肥胖模型瘦素、体内脂肪含量及分布的影响。方法 4周龄C57BL/6小鼠60只,随机分为正常对照组(n=15)和高脂喂养组(n=45)。高脂喂养组给予40%脂肪含量高脂饲料喂养,正常对照组给予普通饲料喂养,构建肥胖小鼠模型至20周龄时,将造模成功的高脂喂养组随机分为利拉鲁肽组、饮食干预组(普通饲料喂养)和继续高脂喂养组(高脂饲料喂养),每组15只。利拉鲁肽组腹腔注射利拉鲁肽(稀释于双蒸水中)[100μg/(kg·d)],饮食干预组、继续高脂喂养组和正常对照组腹腔注射生理盐水[0.017 m L/(kg·d)]。监测记录各组体质量。药物干预12周后于10%水合氯醛麻醉下处死全部小鼠,利用磁共振测定小鼠体内脂肪含量,采用竞争法测定外周血瘦素含量,酶法测定外周血血脂水平。结果利拉鲁肽组体质量最低,与正常对照组、饮食干预组、继续高脂喂养组相比差异有统计学意义(P<0.05);利拉鲁肽组瘦素水平下降,与饮食干预组、继续高脂喂养组差异有统计学意义(P<0.05);利拉鲁肽组血脂水平下降,甘油三酯含量与正常对照组、继续高脂喂养组相比差异有统计学意义(P<0.05),总胆固醇含量仅与继续高脂喂养组差异有统计学意义(P<0.05);利拉鲁肽组脂肪总含量、肠系膜脂肪、附睾脂肪、肾周脂肪、肩胛下脂肪、皮下脂肪与其他各组比较均差异有统计学意义(P<0.05)。结论利拉鲁肽可明显减轻肥胖小鼠的体质量、降低瘦素水平,有降脂和调节脂肪分布的作用。

Objective To observe the effect of liraglutide on the distribution of leptin and fat in high-fat diet induced C57 BL /6 obese mice model. Methods A total of 60 C57 BL /6 mice aged 4 weeks,body weight（ 14. 03 ＋ 0. 92） g were randomly divided into 2 groups： high-fat diet（ 40% fat） group（ n = 45） and normal chowdiet（ 4% fat） group（ n = 15）. The body weight was recorded once a week until the obese mice models were built. Then the 45 obese mice in the high-fat diet group models were randomly divided into 3 groups： liraglutide group[intraperitoneal injection of 100μg /（ kg·d）,n = 15 ],transferred normal diet group[intraperitoneal injection of 0. 017 m L /（ kg·d）,n = 15） ] and high fat diet group（ n = 15）. During the 12-week intervention,the body weight of all animals was recorded. The fat content and leptin were monitored by magnetic resonance imaging and enzyme-linked immunosorbent assay. Results The liraglutide group had the lowest body weight than the other 3 groups（ P〈0. 05）. The liraglutide group had reduced degree of leptin compared with transferred normal diet group and high fat diet group（ P〈0. 05）. The liraglutide grouphad lower serum lipid level; the triglycerides level was significantly lower than that in the normal chowdiet group and high fat diet group（ P〈0. 05）; and the total cholesterol level was significantly lower than that in high fat diet group（ P〈0. 05）. The liraglutide group was different from the other groups in the mesenteric,epididymal,perirenal,subscapular and subcutaneous fat（ P〈0. 05）. Conclusion Liraglutide can significantly reduce the body weight and leptin degree in obese mice and has an effect on regulating lipid and fat distribution.