Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism

Biochem Biophys Res Commun. 1998 Oct 9;251(1):313-9. doi: 10.1006/bbrc.1998.9473.


The liver is a target for bacterial lipopolysaccharide (LPS) and participates in the metabolic response to endotoxemia. Recently published evidence indicates that LPS increases the expression of mitochondrial uncoupling protein-2 (UCP-2) mRNAs in several tissues, including the liver. Because hepatocytes in the healthy liver do not express UCP-2, LPS was thought to induce UCP-2 in liver macrophages, which express UCP-2 constitutively. However, the present studies of cultured peritoneal macrophages indicate that LPS reduces steady state levels of UCP-2 mRNAs in these cells. In contrast, UCP-2 mRNAs are induced in hepatocytes isolated from LPS treated rats and transfection of these hepatocytes with UCP-2 promoter-reporter constructs demonstrates substantial increases in UCP-2 promoter activity. LPS induction of hepatocyte UCP-2 expression is virtually abolished by prior treatment of rats with neutralizing antibodies to tumor necrosis factor alpha (TNF). Futhermore, TNFalpha treatment induces UCP-2 mRNA accumulation in primary cultures of hepatocytes from healthy rats. Thus, hepatocytes are likely to be important contributors to endotoxin-related increases in liver UCP-2 via a mechanism that involves the LPS-inducible cytokine, TNFalpha.

MeSH terms

  • Animals
  • Blotting, Northern
  • Ion Channels
  • Lipopolysaccharides / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Membrane Transport Proteins*
  • Mice
  • Mice, Obese
  • Mitochondrial Proteins*
  • Protein Biosynthesis*
  • RNA / analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / physiology*
  • Uncoupling Agents / metabolism*
  • Uncoupling Protein 2


  • Ion Channels
  • Lipopolysaccharides
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Ucp2 protein, mouse
  • Ucp2 protein, rat
  • Uncoupling Agents
  • Uncoupling Protein 2
  • RNA