Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-alpha and lipopolysaccharide

J Clin Invest. 1996 Jan 1;97(1):37-46. doi: 10.1172/JCI118404.


Although elevated plasma plasminogen activator inhibitor 1 (PAI-1) is associated with obesity, very little is known about its tissue or cellular origin, or about the events that lead to increased PAI-1 levels under obese conditions. Since TNF-alpha is increased in rodents both during obesity and in response to endotoxin treatment, we examined the effects of these agents on PAI-1 gene expression in the adipose tissue of CB6 mice. In untreated mice, PAI-1 mRNA was detected in both mature adipocytes and in stromal vascular cells. Both TNF-alpha and endotoxin significantly increased PAI-1 mRNA in the adipose tissue, peaking at 3-8 h. In situ hybridization analysis of adipose tissue from untreated mice revealed a weak signal for PAI-1 mRNA only in the smooth muscle cells within the vascular wall. In contrast, after endotoxin or TNF-alpha treatment, PAI-1 mRNA also was detected in adipocytes and in adventitial cells of vessels. Endotoxin also induced PAI-1 in endothelial cells, while TNF-alpha additionally induced it in smooth muscle cells. Mature 3T3-L1 adipocytes in culture also expressed PAI-1 mRNA, and its rate of synthesis was also upregulated by TNF-alpha. These studies suggest that the adipose tissue itself may be an important contributor to the elevated PAI-1 levels observed in the plasma under obese conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipocytes / chemistry
  • Adipose Tissue / metabolism*
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Gene Expression Regulation / drug effects*
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / chemistry
  • Muscle, Smooth, Vascular / cytology
  • Plasminogen Activator Inhibitor 1 / analysis
  • Plasminogen Activator Inhibitor 1 / genetics*
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Lipopolysaccharides
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha