ACE2/Ang(1-7)对小鼠脂肪组织脂肪合成的影响

Effect of angiotensin-converting enzyme 2 and angiotensin (1-7) on lipogenesis in white adipose tissue of mice

目的探讨血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)-血管紧张素(1-7)[angiotensin(1-7),Ang(1-7)]对小鼠脂肪组织脂肪合成的影响。方法选取雄性ACE2基因敲除模型小鼠及野生C57BL/6(wild-type,WT)对照小鼠,测体质量,计算体脂率,测定血清三酰甘油(triglycerides,TG)及总胆固醇(total cholesterol,TC)浓度,HE染色观察附睾脂肪细胞形态学变化,蛋白印记(Western blotting)法检测附睾脂肪组织脂肪合成因子乙酰辅酶A羧化酶α(acetyl-Co A carboxylaseɑ,ACCα)、脂肪酸合成酶(fatty acid synthetase,FAS)及脂肪型脂肪酸结合蛋白(adipocyte fatty acid binding protein,a P2)的表达。将雄性db/db小鼠采用数字表法随机分为3组,分别给予0.9%(质量分数)氯化钠注射液,Ang(1-7),Ang(1-7)+A779[Ang(1-7)的拮抗剂]皮下泵入干预4周。测体质量,Western blotting法检测小鼠附睾脂肪组织脂肪合成因子蛋白的表达。结果 ACE2基因敲除小鼠体脂率及血TG浓度明显高于野生对照小鼠。Western blotting法检测结果表明ACE2基因敲除小鼠附睾脂肪组织脂肪合成因子ACCα及FAS蛋白表达明显高于野生对照组。应用Ang(1-7)干预2型糖尿病db/db小鼠显著抑制其附睾脂肪组织脂肪合成因子ACCα及FAS蛋白表达,而应用Ang(1-7)拮抗剂A779拮抗了这一作用。结论 ACE2/Ang(1-7)抑制白色脂肪合成,其机制可能是通过抑制脂肪合成相关因子的表达发挥作用。

Objective To identity the effect of angiotensin-converting enzyme 2（ACE2） and angiotensin（1-7）（Ang（1-7）） on lipogenesis in white adipose tissue of mice. Methods Male ACE2-knockout（ACE2KO） mice and C57 BL/6（wild-type,WT） mice were chosen. The body weight,body fat percentage,total serum cholesterol,and triglycerides were measured. Hematoxylin and eosin staining was employed to observe the morphology changes of epididymal adipocyte. The protein expression of lipogenesis related genes including acetyl-Co A carboxylase ɑ（ACCɑ）,fatty acid synthetase（FAS） and adipocyte fatty acid binding protein（aP2） in epididymal adipose tissue was assayed by Western blotting. Male db/db mice were randomly divided into three groups. Mice were treated with normal saline（NS）,A779[D-Ala7-Ang（1-7）,Ang（1-7） antagonist],and Ang（1-7） ＋ A779[Ang（1-7） antagonist] for 28 days using the micro-osmotic pump. The body weight was measured,and the protein expression of lipogenesis related genes in epididymal adipose tissue was assayed by Western blotting. Results The body fat percentage and serum triglycerides in ACE2KO mice were higher than those in WT mice. The protein expression of ACCɑ and FAS was increased in ACE2KO mice epididymal adipose tissue than control mice.In db/db mice,Ang（1-7） treatment downregulated the protein expression of ACCɑ and FAS in epididymal adipose tissue,A779 inhibited the effect. Conclusion ACE2/Ang（1-7） may inhibit lipogenesis in white adipose tissue by reduction of lipogenesis-related genes.