Cell Biochemistry and Function (2004) 22:1-6

Kupffer cell-derived prostaglandin E2 is involved in regulation of lipid synthesis in rat liver tissue

Audrey M. Neyrinck, Sabrina Margagliotti, Cristina Gomez, Nathalie M. Delzenne

Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Département des Sciences Pharmaceutiques, Université Catholique de Louvain, Brussels, Belgium
email: Nathalie M. Delzenne (delzenne@pmnt.ucl.ac.be)


Abstract
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 E2 (PGE2) release inside liver tissue, a phenomenon contributing to lipid accumulation in hepatocytes. PGE2 secretion as well as lipid synthesis were assessed in precision-cut liver slices (PCLS) from rats previously treated with Kupffer cell inhibitors (GdCl3 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 PGE2 (0.01, 1 and 10 M). Inhibition of Kupffer cell activity by GdCl3 decreases PGE2 secretion by PCLS and resulted in a higher lipid synthesis. Since incubation with PGE2 over 48 h decreases lipid synthesis from acetate in cultured hepatocytes, we propose that the lower PGE2 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.