Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice

World J Gastroenterol. 2006 Jun 7;12(21):3352-8. doi: 10.3748/wjg.v12.i21.3352.

Abstract

Aim: To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide (LPS) -induced liver injury.

Methods: D-galactosamine (GalN) and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with LPS.

Results: In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-alpha (TNF-alpha) and significantly reduced IL-10 levels compared with wild type mice. TNF-alpha gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-alpha levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without adiponectin-pre-treatment.

Conclusion: Adiponectin supresses TNF-alpha production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.

MeSH terms

  • Adiponectin / genetics*
  • Adiponectin / physiology
  • Alanine Transaminase / blood
  • Alanine Transaminase / genetics
  • Animals
  • Cells, Cultured
  • Galactosamine / adverse effects*
  • Galactosamine / pharmacology
  • Gene Expression Regulation / drug effects
  • Interferon-gamma / analysis
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Kupffer Cells / chemistry
  • Kupffer Cells / drug effects
  • Kupffer Cells / physiology
  • Lipopolysaccharides / adverse effects*
  • Lipopolysaccharides / pharmacology
  • Liver / chemistry
  • Liver / drug effects
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adiponectin
  • Receptors, Cell Surface / analysis
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Adiponectin
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, Adiponectin
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • adiponectin receptor 1, rat
  • adiponectin receptor 2, rat
  • Interleukin-10
  • Galactosamine
  • Interferon-gamma
  • Alanine Transaminase