Regulation and physiological actions of the renin-angiotensin system in adipocytes

This dissertation study was designed to investigate the regulation and physiological actions of the renin-angiotensin system in adipose tissue. Adipose cells synthesize and secrete the vasoactive hormone Angiotensin II (Ang II). Classical, circulating Ang II actions involve pressor effects and hemodynamic regulation. In adipose tissue, however, indirect evidence suggests that Ang II modulates adiposity; however no previous studies have directly tested this possibility. In addition little is known about regulation of the renin-angiotensin system in adipose tissue. We addressed each of these issues using adipose tissue from humans and rodents and in adipocyte cell lines maintained in vitro. We first developed a model that allowed us to conduct these experiments in isolated human adipose cells. We then identified various physiological factors, including insulin and adrenergic nervous system stimulation, that regulate expression of the renin- angiotensin system in adipocytes. Subsequently we demonstrated the presence of and characterized the Ang II receptor found in adipose cells. Finally we established that Ang II can directly increase lipid synthesis and storage in both murine and human adipocytes. Our findings indicate that the renin-angiotensin system in adipose tissue is subject to hormonal regulation. Subsequent modulation of local Ang II synthesis could then influence adiposity through the effects of Ang II on lipid synthesis and storage in adipocytes. These studies indicate that the physiological role of Ang II produced by adipocytes involves control of fat mass and may thus play a role in obesity.