Inhibition of Kupffer cell activity induces hepatic triglyceride synthesis in fasted rats, independent of lipopolysaccharide challenge

Background: Lipopolysaccharides (LPS), cleared from the blood by Kupffer cells, induce hypertriglyceridemia. Aims: To test the hypothesis that GdCl3, through inhibition of large Kupffer cell activity, modulates LPS-induced hyperlipidemia in rats. Methods: Male Wistar rats received a single intravenous injection of GdCl3 (10 mg/kg) or saline, 24 h before intraperitoneal LPS (1.5 mg/kg) administration. Serum and hepatic lipids as well as activity of key enzymes controlling fatty acid synthesis and esterification in liver tissue were measured. The incorporation of labeled precursors into lipids was assessed in cultured precision-cut liver slices. Results: GdCl3 does not prevent hypertriglyceridemia occurring in LPS-treated rats. Surprisingly, GdCl3 per se is able to promote triglycerides accumulation in the liver tissue, an effect related to an increase in hepatic fatty acid esterification. Such an effect also occurs in rats receiving a dietary supplementation with glycine (5%) known to inhibit Kupffer cell secretory capacity. Conclusions: Large Kupffer cell inhibition does not prevent LPS-induced hypertriglyceridemia and even leads to a metabolic shift of fatty acids towards their esterification and accumulation in the liver tissue, suggesting that Kupffer cells play a role in the regulation of lipid metabolism of the adjacent hepatocytes, independent of any inflammatory stimulus