Angiotensinogen (ACT), the substrate from which the hypertensive hormone angiotensin II is formed was previously shown to be elevated in adipose tissue from obese (ob/ob and db/db) mice. It is unknown however, whether elevation of adipocyte AGT can be extended to other models of obesity and if hormonal or nutritional factors directly regulate AGT expression in adipocytes. We addressed these issues by analyzing AGT mRNA levels in adipose tissue form obese Zucker rats, viable yellow A mice and humans and in cultured murine 3T3-L1 and human adipocytes treated with lipogenic and lipolytic nutrients and hormones. We demonstrate that AGT mRNA is decreased by 50 and 80% respectively in adipose tissue from obese vs lean Zucker rats and Avy mice. Furthermore AGT mRNA is expressed at various levels in human adipose tissue however this difference disappears in cultured cells. Moreover, unlike other lipid metabolizing genes induced during adipocyte differentiation such as fatty acid synthase and stearoyl CoA desaturase, AGT was neither regulated by glucose nor by linoleic acid. Finally we demonstrate that 10 nM insulin significantly increases AGT mRNA content (p<0.01), while 10 nM isoproterenol significantly decreases AGT mRNA level (p<0.01). These data suggest that insulin and isoproterenol are potential modulators of AGT levels, however other as yet unidentified factors may contribute to regulation of this gene in vivo.
|Published - 1997