REGULATION BY FATTY-ACIDS OF ANGIOTENSINOGEN GENE-EXPRESSION IN PREADIPOSE CELLS

Adipocytes represent an important source of angiotensinogen (AT). Angi otensin II (A-II) stimulates in vitro and in vivo the formation and re lease of prostacyclin which acts as a potent adipogenic signal in trig gering the terminal differentiation of preadipocytes into adipocytes [ Darimont, Vassaux, Gaillard, Ailhaud and Negrel (1994) Int. J. Obes. 1 8, 783-788], Since fatty acids have been reported to activate in pread ipose cells the expression of various differentiation-dependent genes, the role of fatty acids in the regulation of AT gene expression was i nvestigated. Long-chain natural and non-metabolized fatty acids as wel l as peroxisome proliferators behave as activators of AT gene expressi on. Accumulation of AT mRNA parallels that of the adipocyte fatty acid -binding protein gene and is primarily due to transcriptional activati on of the AT gene, AT mRNA decreases after fatty acid removal (half-li fe approx. 8 h). Secretion of AT is also observed but appears mainly a s a late differentiation-dependent phenomenon, Thus the AT gene appear s to be a fatty acid-responsive gene; this regulation provides a poten tial link between the flux of fatty acids and the potential of adipose tissue to produce AT and possibly A-II.