Insulin down-regulates angiotensinogen gene expression and angiotensinogen secretion in cultured adipose cells

Adipose tissue is an important source of angiotensinogen (AT) after liver, Since an association exists between body mass index, hypertension, and insulin-resistance, the role of insulin on the regulation of AT gene expression and AT secretion was examined in cultured Ob1771 and 3T3-F442A adipose cells, Within a physiological range of concentrations (1-17 nM), insulin exerted a negative effect on the abundance of AT mRNA and the secretion of AT. Alterations of insulin-resistance by treatment of adipose cells with TNF-alpha or the thiazolidinedione BRL49653 led respectively to a decrease or an increase in the potency of insulin to down-regulate AT gene expression, whereas maximal inhibition by insulin increased from 30% in TNF alpha-treated cells to 60% in BRL49653-treated cells. These results suggest that a potential link between insulin resistance and high blood pressure may exist by means of increased AT secretion from adipose tissue, especially in obese subjects. (C) 1998 Academic Press.