Kupffer cell‐derived prostaglandin E 2 is involved in regulation of lipid synthesis in rat liver tissue

Our recent studies suggest that Kupffer cells play a role in the physiological regulation of lipid metabolism of the adjacent hepatocytes. In the present study, we have tested the hypothesis that inhibition of Kupffer cells decreases prostaglandin E 2 (PGE 2 ) release inside liver tissue, a phenomenon contributing to lipid accumulation in hepatocytes. PGE 2 secretion as well as lipid synthesis were assessed in precision‐cut liver slices (PCLS) from rats previously treated with Kupffer cell inhibitors (GdCl 3 10 mg kg −1 body wt, i.v. injection and glycine 5% in diet). In addition, lipid synthesis was assessed in primary rat hepatocytes cultured in the absence or presence of PGE 2 (0.01, 1 and 10 μ M ). Inhibition of Kupffer cell activity by GdCl 3 decreases PGE 2 secretion by PCLS and resulted in a higher lipid synthesis. Since incubation with PGE 2 over 48 h decreases lipid synthesis from acetate in cultured hepatocytes, we propose that the lower PGE 2 secretion linked to Kupffer cell inhibition, partly explains a higher rate of synthesis of lipids with a subsequent accumulation in liver tissue, as previously shown in fasted rats. Copyright © 2004 John Wiley & Sons, Ltd.