Influence of membrane-bound tumor necrosis factor (TNF)-alpha on obesity and glucose metabolism

J Thromb Haemost. 2004 Mar;2(3):507-13. doi: 10.1111/j.1538-7933.2004.00612.x.


Objectives: To investigate the influence of transmembrane tumor necrosis factor (TNF)-alpha on adipose tissue development and insulin-mediated glucose metabolism.

Methods and results: TNF-alpha and lymphotoxin-alpha-deficient mice expressing non-cleavable transmembrane TNF-alpha (Tg-tmTNF-alpha) and TNF-alpha/lymphotoxin-alpha double knockout (control) mice were kept on high-fat diet for 15 weeks. The food intake and feeding efficiency of Tg-tmTNF-alpha mice were significantly higher compared with control mice. At the end of the study, Tg-tmTNF-alpha mice had a significantly higher total body weight, as well as subcutaneous and gonadal adipose tissue mass. Histological analysis revealed that the expression of Tg-tmTNF-alpha resulted in a significantly increased adipocyte area and blood vessel density. Plasma leptin levels correlated positively with adipose tissue mass. The plasma levels of total cholesterol and HDL-cholesterol were significantly increased and LDL-cholesterol levels significantly decreased in Tg-tmTNF-alpha mice. Fasting blood glucose and plasma insulin levels were not different between the two genotypes and intraperitoneal glucose and insulin tolerance tests did not show significant differences.

Conclusions: Transmembrane TNF-alpha enhances adipose tissue formation without altering insulin-mediated glucose metabolism in mice with nutritionally induced obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / physiopathology*
  • Animals
  • Base Sequence
  • Blood Glucose / metabolism*
  • Blood Vessels / drug effects
  • Blood Vessels / physiology
  • Body Weight / drug effects
  • Cell Membrane / metabolism
  • DNA Primers
  • Glucose Tolerance Test
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Obesity / physiopathology*
  • RNA, Messenger / genetics
  • Tumor Necrosis Factor-alpha / deficiency
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / pharmacokinetics
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Blood Glucose
  • DNA Primers
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha