White adipose tissue and liver are important angiotensinogen (AGT) producti
on sites. Until now, plasma AGT was considered to be a reflection of hepati
c production. Because plasma AGT concentration has been reported to correla
te with blood pressure, and to be associated with body mass index, we inves
tigated 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 t
issue. 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 AG
T-deficient mice. Our results show that in both genotypes, targeted express
ion of AGT in adipose tissue increases fat mass. Mice whose AGT expression
is restricted to adipose tissue have AGT circulating in the blood stream, a
re normotensive, and exhibit restored renal function compared with AGT-defi
cient mice. Moreover, mice that overexpress adipose AGT have increased leve
ls 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.