脂肪细胞型脂肪酸结合蛋白疫苗对高脂喂养雌鼠体重和糖耐量的影响

目的:构建能诱导出针对脂肪细胞型脂肪酸结合蛋白(FABP4)特异性中和抗体的疫苗,为高脂诱导下肥胖和胰岛素抵抗的防治新途径提供理论和实验依据。方法:野生型C57BL/6J雌鼠随机分为疫苗组(n=10,高脂饲养)、佐剂组(n=10,高脂饲养)和空白对照组(n=10,普通饲养),分别予以皮下注射生物合成的FABP4蛋白、佐剂和磷酸盐缓冲液,观察比较各组抗体滴度、安全耐受性和体重、摄食量、空腹血糖、胰岛素抵抗指数(HOMA-IR)、糖耐量实验血糖曲线下面积(AUC)等指标。结果:疫苗组小鼠产生了高滴度的FABP4特异性抗体,并于第3轮加强免疫后达到平衡状态。首次免疫16周后,疫苗组小鼠体重高于空白对照组,但明显低于佐剂组(P<0.05);日平均摄食量高于空白对照组(P<0.05),与佐剂组无差异(P>0.05);空腹血糖、HOMA-IR、腹腔葡萄糖耐量实验AUC均明显低于佐剂组(P<0.05),与对照组无统计学差异(P>0.05)。结论:以FABP4作为抗原免疫小鼠,可产生高滴度特异性抗体IgG,有效降低高脂喂养野生型雌性小鼠体重、空腹血糖、HOMA-IR和血糖AUC等指标,为高脂诱导的肥胖和胰岛素抵抗的治疗提供了新的途径和初步证据,可进行深入研究。

Effect of Vaccination Against Adipocyte Fatty Acid Binding Protein on Body Weight and Glucose Tolerance in Female Mice with HighFat Diet

Objective: To construct vaccine against adipocyte fatty acid binding protein(FABP4) in order to give theoretical and experimental evidence on prevention and cure of high-fat-induced obesity and insulin resistance.Methods: 30 wild-type female C57BL/6J mice were randomly divided into vaccine group(VG,n=10,with high-fat diet),adjuvant group(AG,n=10,with high-fat diet) and control group(CG,n=10,with normal diet),and were sub cutaneously injected with biosynthetic FABP4,adjuvant,and phosphate buffered solution,respectively.Several index es were observed,including antibody titers,security and tolerance,body weight,food intake,fasting blood glucose,homeostasis model of assessment-insulin resistance(HOMA-IR) index,glucose area under concentration-time curve(AUC) of intraperitoneal glucose tolerance test(IPGTT).Results: Mice in VG responsed with high peptide-specif ic FABP4 antibody titers,which were stable after the 3rd booster.Sixteen weeks after the first immunization,the body weight in VG was higher than that in CG but much lower than that in AG(P<0.05).Food-intake was high er than that in CG(P<0.05),and had no difference with that in AG(P>0.05).The levels of fasting blood glucose,HOMA-IR index,glucose AUC of IPGTT were all lower than those in AG(P<0.05),and had no differences with those in CG(P>0.05).Conclusion: FABP4 as a kind of antigen to immune mice induces high titer of specific an tibody,which can effectively reduce body weight,fasting blood glucose,HOMA-IR index and glucose AUC in wild-type female mice with high-fat diet.Our study offers a new target and preliminary evidence in therapy of high-fat-induced obesity and insulin resistance,which needs further in-depth researches.