Precision-cut liver slices in culture as a tool to assess the physiological involvement of Kupffer cells in hepatic metabolism

Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Département des Sciences Pharmaceutiques, Université Catholique de Louvain, PMNT-UCL 73 avenue Mounier, B-1200 Brussels, Belgium.
Comparative Hepatology (Impact Factor: 1.88). 02/2004; 3 Suppl 1:S45. DOI: 10.1186/1476-5926-2-S1-S45
Source: PubMed
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the role of Kupffer cell in glucose metabolism and hepatic insulin sensitivity in mice. Both phagocytic activity and secretory capacity of Kupffer cells were blunted 24h after GdCl3 administration. Glucose tolerance--evaluated following an oral glucose tolerance test (OGTT)--was higher in GdCl3-treated mice whereas fasting insulinemia and HOMA-IR index decreased. The improvement of glucose tolerance and hepatic insulin signalling pathway after inhibition of Kupffer cells was supported by a lower hepatic gluconeogenic enzyme expression and a higher phosphorylation of Akt upon insulin challenge. Moreover, fasting hyperglycemia, insulin resistance and impaired glucose tolerance--induced by high fat (HF) diet--were improved through chronic administration of GdCl3. Interestingly, the inhibition of Kupffer cell exerted antiobesity effects in HF-fed mice, and lowered hepatic steatosis. Therefore, strategies targeting Kupffer cell functions could be a promising approach to counteract obesity and related metabolic disorders.
    Biochemical and Biophysical Research Communications 08/2009; 385(3):351-6. DOI:10.1016/j.bbrc.2009.05.070 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we tested the hypothesis that dietary oligofructose (FOS) can modulate both the response to an endotoxic shock induced by lipopolysaccharide (LPS) administration and the activity of resident hepatic macrophages, i.e., Kupffer cells. Male Wistar rats (n = 5-9 per group) were fed a standard diet or a diet supplemented with 10 g/100 g FOS for 3 wk. LPS (10 mg/kg) or saline were injected i.p. after dietary treatment. After LPS injection, serum levels of tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, and prostaglandin E(2) (PGE(2)), an immunosuppressive mediator, were higher in FOS-treated rats than in control rats. Alanine aminotransferase (ALT) activity was approximately 50% lower than in controls 24 h after LPS administration in FOS-treated rats, suggesting less hepatic injury; this was confirmed through histological analysis. FOS treatment increased the number of large phagocytic Kupffer cells, as assessed by histological examination of the liver after colloidal carbon injection into the portal vein. Precision-cut liver slices (PCLS) from FOS-treated rats released more TNF-alpha and PGE(2) into the incubation medium than PCLS from control rats, independently of LPS challenge in vitro. This would suggest that the higher Kupffer cell phagocytic activity and secretion capacity due to FOS supplementation improve LPS clearance in liver tissue and reduce hepatocyte alterations. This study supports the hypothesis that oligofructose might decrease liver tissue injury after endotoxic shock and sepsis.
    Journal of Nutrition 06/2004; 134(5):1124-9. · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the role of inflammatory mediators in the hepatoprotective effect of glycine against lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were used (N = 4 or 5 per group). Precision-cut liver slices (PCLS) were prepared for in vitro studies. Glycine (10 mM) and LPS (10 mug/ml) were added to the incubation medium of PCLS obtained 3 h after LPS intraperitoneal (i. p.) administration (10 mg/kg) or saline injection to rats. Glycine effects were also investigated in vivo by treating rats with a diet containing glycine (5%) during 3 days. Tissue injury was assessed by measuring adenosine triphosphate (ATP) and glycogen contents of liver tissue as well as by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activity in the medium (in vitro) or in the serum (in vivo). Tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2)(PGE(2)) and NOx (reflecting nitric oxide production) were measured in the incubation medium or in the serum. Histological detection of both ED-2 and peroxidase activity were used as Kupffer cell markers. Student t test or two-way ANOVA were used for statistic analysis. Glycine added to the culture medium increased both ATP and glycogen contents of PCLS from LPS-treated rats, reduced the production of TNF-alpha and NOx whereas PGE(2) secretion by PCLS increased. In contrast to the in vitro effect of glycine, we observed that a glycine-enriched diet decreased PGE(2) secretion in the serum after LPS challenge. The effect of glycine on LPS-induced mediator secretion is different considering in vitro or in vivo situations. Interestingly, glycine in vitro is able to prevent energy status depletion of PCLS occurring upon inflammation, a phenomenon probably linked to change in inflammatory mediator secretion pattern by hepatic immune cells, namely Kupffer cells.
    Inflammation Research 04/2005; 54(3):106-12. DOI:10.1007/s00011-004-1330-9 · 2.14 Impact Factor

Preview (3 Sources)

Available from