Deficiency of angiotensinogen in hepatocytes markedly decreases blood pressure in lean and obese male mice.

We recently demonstrated that adipocyte deficiency of angiotensinogen (AGT) ablated high-fat diet-induced elevations in plasma angiotensin II (Ang II) concentrations and obesity-hypertension in male mice. Hepatocytes are the predominant source of systemic AGT. Therefore, in this study, we defined the contribution of hepatocyte-derived AGT to obesity-induced elevations in plasma AGT concentrations and hypertension.

Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism.

We recently demonstrated that female mice are resistant to the development of obesity-induced hypertension through a sex hormone-dependent mechanism that involved adipose angiotensin-converting enzyme 2 (ACE2). In this study, we hypothesized that provision of 17β-estradiol (E2) to ovariectomized (OVX) high-fat (HF)-fed female hypertensive mice would reverse obesity-hypertension through an ACE2-dependent mechanism. Pilot studies defined dose-dependent effects of E2 in OVX female mice on serum E2 concentrations and uterine weights.

Angiotensin II Stimulates Sympathetic Neurotransmission to Adipose Tissue.

Angiotensin II (AngII) facilitates sympathetic neurotransmission by regulating norepinephrine (NE) synthesis, release and uptake. These effects of AngII contribute to cardiovascular control. Previous studies in our laboratory demonstrated that chronic AngII infusion decreased body weight of rats.

Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice.

Previous studies demonstrated that overexpression of angiotensinogen (AGT) in adipose tissue increased blood pressure. However, the contribution of endogenous AGT in adipocytes to the systemic renin-angiotensin system (RAS) and blood pressure control is undefined. To define a role of adipocyte-derived AGT, mice with loxP sites flanking exon 2 of the AGT gene (Agt(fl/fl)) were bred to transgenic mice expressing Cre recombinase under the control of an adipocyte fatty acid-binding protein 4 promoter (aP2) promoter to generate mice with adipocyte AGT deficiency (Agt(aP2)).

ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet.

Adipose tissue expresses components of the renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE2), a new component of the RAS, catabolizes the vasoconstrictor peptide ANG II to form the vasodilator angiotensin 1-7 [ANG-(1-7)]. We examined whether adipocytes express ACE2 and its regulation by manipulation of the RAS and by high-fat (HF) feeding.

Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes.

Adipocytes secrete a variety of factors, including angiotensinogen, the only known precursor to Angiotensin II (AngII). Recent studies suggest that adipocyte-derived angiotensinogen can contribute to circulating angiotensinogen concentrations and modulate blood pressure; however, an autocrine role for adipocyte-derived angiotensinogen and/or AngII has not been well defined. We sought to determine whether locally produced AngII influences the release of leptin from adipocytes and thus circulating leptin concentrations.