胰高血糖素样肽1受体激动剂exendin-4增加高脂喂养的C57BL/6J小鼠棕色脂肪脂代谢
Exendin-4 improves fat metabolism of brown adipose tissue in high-fat diet-induced obese C57BL/6J mice
摘要目的:观察胰高血糖素样肽1(GLP-1)受体激动剂exendin-4干预对高脂饮食喂养的C57BL/6J小鼠棕色脂肪脂代谢的影响。方法将30只健康雄性6周龄C57BL/6J小鼠采用随机数字法分为正常组、高脂组、exendin-4干预组,每组10只。高脂组给予高脂饲料喂养、exendin-4干预组给予高脂饲料喂养联合exendin-4皮下注射。16周后,测定各组体重、体脂含量、游离脂肪酸、瘦素、甘油三酯水平,同时利用实时定量PCR和Western blotting法检测各组小鼠肩胛棕色脂肪葡萄糖转运体4(GLUT-4)、过氧化物酶体增殖剂激活受体γ2(PPAR-γ2)、脂滴包被蛋白(perilipin)和解偶联蛋白1(UCP-1) mRNA及蛋白表达。多组间数据比较采用单因素方差分析,两组间比较采用t检验。结果与正常组相比,高脂组小鼠体重、体脂成分、游离脂肪酸、瘦素、甘油三酯的水平明显升高(t=7.34、6.11、8.33、10.51、4.19,均P<0.05);且高脂组肩胛棕色脂肪GLUT-4、PPAR-γ2、perilipin和UCP-1的基因和蛋白表达均显著下降(t=7.15~34.79,均P<0.05)。与高脂组相比,exendin-4干预组小鼠体重、体脂成分、游离脂肪酸、瘦素、甘油三酯均较高脂组显著降低(t=5.63、4.04、8.85、6.06、3.07,均P<0.05),同时exendin-4干预组小鼠肩胛棕色脂肪GLUT-4、PPAR-γ2、perilipin和UCP-1基因和蛋白表达均较高脂组显著升高(t=5.38~21.69,均P<0.05)。结论 GLP-1受体激动剂可能通过调控棕色脂肪脂代谢而影响体重。
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abstractsObjective To investigate the role of exendin-4 treatment on fat metabolism of brown adipose tissue in C57BL/6J mice induced with high-fat diet. Methods Thirty six-week-old C57BL/6J mice were randomly divided into 3 groups(10 mice in each group):control group, high-fat diet (HFD) group, and HFD group treated with exendin-4. After 16 weeks, the body weight, body fat composition, free fatty acids, leptin, triglycerides level of each group were measured. The mRNA and protein expression of glucose transporter type 4 (GLUT-4), peroxisome proliferative activated receptor γ2(PPAR-γ2), perilipin and uncoupling protein 1(UCP-1) in the scapular brown adipose tissue were detected with real-time quantitative polymerase chain reaction(PCR) and Western blotting methods. One-way ANOVA was used when data were compared among multiple groups and t analysis was applied for comparison between two groups. Results Compared with those in control group, the body weight, body fat composition, free fatty acids, leptin and triglyceride levels increased significantly in the HFD group (t=7.34, 6.11, 8.33, 10.51, 4.19, all P<0.05);the mRNA and protein expression of GLUT-4, PPAR-γ2, perilipin and UCP-1 in the scapular brown adipose tissue in HFD group decreased significantly when compared with those in control group (t=7.15-34.79, all P<0.05). Compared with those in the HFD group, the body weight, body fat composition, free fatty acids, leptin and triglyceride levels decreased significantly in the exendin-4-treating group(t=5.63, 4.04, 8.85, 6.06, 3.07, all P<0.05), while the mRNA and protein expression of GLUT-4, PPAR-γ2, perilipin and UCP-1 increased significantly in the scapular brown adipose tissue in the exendin-4-treating group(t=5.38-21.69, all P<0.05). Conclusion GLP-1 receptor agonist may reduce body weight via regulating lipid metabolism in brown fat.
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