Regulation by fatty acids of angiotensinogen gene expression in preadipose cells

Abstract

Adipocytes represent an important source of angiotensiongen (AT). Angiotensin II (A-II) stimulates in vitro and in vivo the formation and release of prostacyclin which acts as a potent adipogenic signal in triggering the terminal differentiation of preadipocytes into adipocytes [Darimont, Vassaux, Gaillard. Ailhaud and Négrel (1994) Int. J. Obes. 18, 783-788]. Since fatty acids have been reported to activate in preadipose cells the expression of various differentiation-dependent genes, the role of fatty acids in the regulation of AT gene expression was investigated. Long-chain natural and non-metabolized fatty acids as well as peroxisome proliferators behave as activators of AT gene expression. Accumulation of AT mRNA parallels that of the adipocyte fatty acid-binding protein gene and is primarily due to transcriptional activation of the AT gene. AT mRNA decreases after fatty acid removal (half-life approx. 8 h). Secretion of AT is also observed but appears mainly as a late differentiation-dependent phenomenon. Thus the AT gene appears to be a fatty acid-responsive gene; this regulation provides a potential link between the flux of fatty acids and the potential of adipose tissue to produce AT and possibly A-II.