Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation
Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation
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DOI：
10.1096/fj.01-0457fje
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Teboul, M
中科院分区：
文献类型：
--
作者：
Massiéra, F;Bloch-Faure, M;Teboul, M
白色脂肪组织和肝脏是重要的血管紧张素原（AGT）产生场所。迄今为止，血浆 AGT 被认为是肝脏生成的反映。据报道，血浆 AGT 浓度与血压相关，并且与体重指数相关，因此我们研究了脂肪 AGT 是否局部释放并进入血流。为此，我们培育了脂肪 AGT 过度表达或 AGT 表达仅限于脂肪组织的转基因小鼠。这是通过使用 aP2 脂肪细胞特异性启动子驱动野生型和低血压 AGT 缺陷小鼠中大鼠 agt cDNA 的表达来实现的。我们的结果表明，在两种基因型中，脂肪组织中 AGT 的靶向表达都会增加脂肪量。 AGT表达仅限于脂肪组织的小鼠的血流中有AGT循环，血压正常，并且与AGT缺陷小鼠相比，肾功能恢复。此外，与野生型小鼠相比，过度表达脂肪 AGT 的小鼠循环 AGT 水平升高，并且患有高血压。这些动物模型表明，脂肪组织产生的 AGT 在局部脂肪组织发育和内分泌系统中发挥作用，这支持了脂肪 AGT 在高血压肥胖患者中的作用。
White adipose tissue and liver are important angiotensinogen (AGT) production sites. Until now, plasma AGT was considered to be a reflection of hepatic production. Because plasma AGT concentration has been reported to correlate with blood pressure, and to be associated with body mass index, we investigated whether adipose AGT is released locally and into the blood stream. For this purpose, we have generated transgenic mice either in which adipose AGT is overexpressed or in which AGT expression is restricted to adipose tissue. This was achieved by the use of the aP2 adipocyte-specific promoter driving the expression of rat agt cDNA in both wild-type and hypotensive AGT-deficient mice. Our results show that in both genotypes, targeted expression of AGT in adipose tissue increases fat mass. Mice whose AGT expression is restricted to adipose tissue have AGT circulating in the blood stream, are normotensive, and exhibit restored renal function compared with AGT-deficient mice. Moreover, mice that overexpress adipose AGT have increased levels of circulating AGT, compared with wild-type mice, and are hypertensive. These animal models demonstrate that AGT produced by adipose tissue plays a role in both local adipose tissue development and in the endocrine system, which supports a role of adipose AGT in hypertensive obese patients.