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.


OBJECTIVE
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.
Neyrinck
Audrey M
AM
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Département des Sciences Pharmaceutiques, Université Catholique de Louvain, 73 Avenue Mounier, B-1200 Brussels, Belgium.
Taper
Henryk S
HS
Gevers
Valérie
V
Declerck
Barbara
B
Delzenne
Nathalie M
NM
D000818:Animals; D002244:Carbon / Q000493:pharmacokinetics; D003102:Colloids / Q000493:pharmacokinetics; D005215:Fasting / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003102:Colloids; D008070:Lipopolysaccharides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002244:Carbon; D005682:Gadolinium; C038958:gadolinium chloride