EFFECTS OF OLEATE AND FATTY-ACIDS FROM OMENTAL ADIPOCYTES ON INSULIN UPTAKE IN RAT-LIVER CELLS

Hyperinsulinemia in central type (upper body) obesity has been related to reduced hepatic insulin uptake caused by fatty acids reaching the portal vein directly from the omental (visceral) fat depot. We investi gated the effect of sodium oleate and fatty acid-rich buffer recovered from incubation of omental adipocytes with 10(-7) m epinephrine on sp ecific [I-125]insulin uptake (at 37 C) in freshly prepared and culture d hepatocytes and nonparenchymal liver cells isolated from 200-250 g r ats. In hepatocytes, insulin uptake was studied after standard cell is olation and washing and after additional repeated 30-min washings at 3 7 C. In the vigorously washed hepatocytes, both fatty acid rich buffer (from 0.08-1.3 mm) and sodium oleate (from 0.0125-1.2 mm) decreased i nsulin uptake maximally by approximately 30% and approximately 40%, re spectively i(P < 0.005); a biphasic effect of fatty acids was observed , with maximal inhibition occurring at 0.08-0.1 mm. Without vigorous w ashing, oleate had no effect on insulin uptake in either freshly prepa red or cultured hepatocytes and nonparenchymal cells. The reason for t he observed inhibitory effect of fatty acids on insulin uptake in vigo rously washed cells remains unknown, but the effect is unlikely to be physiologically important. Thus, our data do not support the hypothesi s that the increased concentration of fatty acids in the portal vein i s responsible for reduced hepatic insulin uptake and hyperinsulinemia in upper body obesity.