多巴胺D2受体基因敲除导致体重减轻以及棕色脂肪PRDM16、UCP1、FAS和ACC的表达变化

Changes of PRDM16, UCP1, FAS and ACC expression of dopamine D2 receptor knockout mice

目的以多巴胺D2受体基因敲除(D2KO)小鼠为动物模型,研究D2KO小鼠体重减轻后,棕色脂肪组织(brown adipose tissue,BAT)重量,白色脂肪重量,BAT中含PR结构域蛋白16(PRD1-BF1-RIZ1 homologous domain containing 16,PRDM16)、解偶联蛋白1(uncoupling protein 1,UCP1)、脂肪酸合酶(fatty acid synthase,FAS)以及乙酰辅酶A羧化酶(acetyl Coenzyme A carboxylase,ACC)的mRNA和蛋白表达变化,以期为肥胖机制研究提供线索。方法 8周龄野生型小鼠组(wild type,WT)和D2KO小鼠组各10只。分别称量各小鼠体重及其白色脂肪、棕色脂肪重量。Real-time quantitative RT-PCR方法检测棕色脂肪中PRDM16、UCP1、FAS、ACC的m RNA表达水平,Western blotting方法检测棕色脂肪中PRDM16、UCP1、FAS、ACC的蛋白表达水平。结果 WT组动物体重为(23.78±0.54)g,D2KO组动物体重为(20.54±1.15)g,P<0.05。WT组动物附睾脂肪(epididymal adipose tissue,eAT)重量为(1.083±0.02)g,D2KO组动物e AT重量为(0.978±0.03)g,P<0.05。WT组动物皮下脂肪(subcutaneous adipose tissue,sAT)重量为(1.85±0.05)g,D2KO组动物sAT重量为(1.72±0.03)g,P<0.05。WT组动物BAT重量为(31.38±4.22)mg,D2KO组动物BAT重量为(42.44±2.47)mg,P<0.05。半定量PCR与Western blotting检测结果显示,相对于WT组,D2KO组小鼠棕色脂肪中PRDM16、FAS、ACC的mRNA与蛋白的表达均显著增加,UCP1的mRNA与蛋白表达显著减少。结论 D2KO小鼠的体重减轻与棕色脂肪中的PRDM16、UCP1、FAS以及ACC存在一定关联。

Objective To observe the expression of PRD1-BF1-RIZ1 homologous domain containing 16(PRDM16),uncoupling protein 1(UCP1),fatty acid synthase(FAS)and acetyl Coenzyme A carboxylase(ACC)in dopamine D2 receptor knockout mice.Methods The body weight and fat mass of wild type group(WT)and dopamine D2 receptor knockout group(D2KO)were compared.Real-time quantitative RT-PCR and Western blotting analysis were used to detect PRDM16,UCP1,FAS and ACC expression in BAT of both groups.Results Body weight of the WT group was(23.78±0.54)g while D2KO group was(20.54±1.15)g.The epididymal adipose tissue(eAT)fat mass was(1.083±0.02)g while the D2KO group was(0.978±0.03)g.The subcutaneous adipose tissue(sAT)fat mass was(1.85±0.05)g while the D2KO group was(1.72±0.03)g.The brown adipose tissue(BAT)fat mass was(31.38±4.22)mg while the D2KO group was(42.44±2.47)mg.Compared with the WT group,the mRNA and protein expression of UCP1 in BAT were significantly decreased in D2KO group while the m RNA and protein expression of PRDM16,FAS,ACC were significantly increased.The m RNA and protein level of ACC did not change between two groups.Conclusion The expression of PRDM16,UCP1,FAS and ACC in BAT may be related to the weight loss of dopamine D2 receptor knockout mice.Compared with the WT group,the mRNA and protein expression of UCP1 in BAT is significantly decreased in D2KO group while the mRNA and protein expression of PRDM16,FAS,ACC is significantly increased.