胰升糖素样肽1受体激动剂对高脂喂养肥胖大鼠胰岛素靶组织中趋化素表达的干预效应

摘要

Objective The present study aimed to investigate the therapeutic impact of glucagon-like peptide 1 receptor agonist liraglutide on chemerin expression in insulin target tissues in high-fat diet-induced obese rats. Methods Male SD rats were fed a high-fat diet for 12 weeks to induce obesity and then administered various doses of liraglutide(0, 50, 100, and 200 μg/kg) twice daily for 4 weeks. Enzyme-linked immunosorbent assay, real-time PCR and Western blot analyses were used to assess serum chemerin, aswell as mRNA and protein levels of chemerin in adipose, liver and skeletal muscle tissues. Results Chemerin expression was significantly higher in serum as well as adipose, liver and skeletal muscle tissues in obese rats as compared to control rats. Liraglutide treatment was sufficient to reduce serum chemerin concentration, its mRNA and protein levels of in adipose and liver tissues but not skeletal muscle. Conclusion The circulating chemerin level is an index which can reflect obesity. We conclude that glucagon-like peptide-1 receptor agonist down-regulates the expression of chemerin and may provide a therapeutic target for obesity-related diseases.%目的：通过研究胰升糖素样肽1受体激动剂利拉鲁肽对肥胖大鼠胰岛素靶组织中脂肪因子趋化素( chemerin)表达水平的影响，评价该药物的干预效应。方法雄性SD大鼠以高脂饲料喂养12周建立肥胖大鼠模型，分别给予不同剂量(0、50、100、200μg/kg )利拉鲁肽每日2次皮下注射干预，为期4周。以ELISA法测定大鼠血清趋化素水平；取大鼠肝脏组织、脂肪组织和骨骼肌组织，分别应用实时PCR和Western印迹方法检测趋化素mRNA和蛋白的表达水平。结果肥胖大鼠血清趋化素水平升高，肝脏组织、脂肪组织和骨骼肌组织中趋化素mRNA和蛋白水平均显著高于对照组(P<0.05)。利拉鲁肽治疗4周，同高脂组比较，干预组大鼠循环趋化素水平下降，肝脏组织、脂肪组织趋化素mRNA和蛋白水平降低(P<0.05)，而骨骼肌组织中趋化素mRNA和蛋白水平降低差异无统计学意义(P>0.05)。结论循环趋化素水平是能够反映肥胖的指标，胰升糖素样肽1受体激动剂能够下调趋化素的表达水平，可能为肥胖相关的代谢性疾病提供新的治疗靶点。