1: J Hepatol  2002 Apr;36(4):466-73 

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

Neyrinck AM, Taper HS, Gevers V, Declerck B, Delzenne NM.

Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement
des Sciences Pharmaceutiques, Universite Catholique de Louvain, 73 Avenue
Mounier, B-1200 Brussels, Belgium.

BACKGROUND: Lipopolysaccharides (LPS), cleared from the blood by Kupffer cells,
induce hypertriglyceridemia. AIMS: To test the hypothesis that GdCl(3), through
inhibition of large Kupffer cell activity, modulates LPS-induced hyperlipidemia
in rats. METHODS: Male Wistar rats received a single intravenous injection of
GdCl(3)(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: GdCl(3) does not prevent
hypertriglyceridemia occurring in LPS-treated rats. Surprisingly, GdCl(3) 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.

PMID: 11943416 [PubMed - indexed for MEDLINE]