Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis

Abstract

Mobilization of FFA in mice, triggered with an injection of thrombin, was followed within 24 h by a 2.5-fold increase in fibrinogen synthesis and a 30% increase in plasma fibrinogen concentration. In mouse liver slices, incubated in plasma, additions of palmitate or stearate in amounts similar to those expected in vivo in FFA mobilization stimulated fibrinogen synthesis 5.6- to 6.1-fold while unsaturated and short-chain FFA were less effective. Palmitate and linoleate also augmented albumin synthesis although not as stongly as fibrinogen synthesis. These observations raised the possibility that the greater effectiveness of saturated FFA in stimulating fibrinogen synthesis may reflect higher FFA/albumin ratios within hepatocytes in the presence of saturated FFA. Injection of exogenous defatted albumin into mice before thrombin injection prevented the FFA-associated rise in fibrinogen synthesis and plasma concentration. In incubated liver slices, defatted albumin abolished the FFA stimulation of fibrinogen synthesis when FFA/albumin ratios were maintained to the physiological range. These studies indicate that the FFA/ALBUMIN RATIO MAY PLAY A MAJOR ROLE IN THE REPLENISHMENT OF FIBRINOGEN AFTER PERIODS OF RAPID DEFIBRINOGENATION.