Diabetologia

, Volume 38, Issue 7, pp 764–771

Effects of tumour necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture

  • H. Hauner
  • Th. Petruschke
  • M. Russ
  • K. Röhrig
  • J. Eckel
Originals

Summary

Tumour necrosis factor alpha (TNFα) has been found to cause a delipidation of fat cells and a decrease of the adipose tissue mass. In the present study, we tried to elucidate some of the mechanisms responsible for this phenomenon by investigating the action of TNFα on specific pathways which are involved in lipid storage. Cultured stromal cells from human adipose tissue were induced to differentiate into adipose cells by exposure to adipogenic factors and subsequently used for studying the effects of TNFα on fat cell metabolism. Presence of 5 nmol/l TNFα for 24 h resulted in a complete loss of the stimulatory effect of insulin on 2-deoxy-glucose transport. This inhibitory action was paralleled by a decrease of GLUT4 protein and mRNA levels. The amount of cellular GLUT4 protein was reduced by 49 ± 3 % after a 24-h exposure and by 82 ± 18 % after a 72-h exposure to 5 nmol/1 TNFα. GLUT4 mRNA was almost undetectable after a 24-h incubation with 5 nmol/l TNFα In a similar time-dependent manner, TNFα dramatically reduced the lipoprotein lipase mRNA content of the cells. Furthermore, incubation of cultured human fat cells with TNFα resulted in a marked dose-dependent stimulation of lipolysis, assessed by glycerol release, by up to 400 % above controls, which became apparent after a 6-h exposure at the earliest. These data suggest that TNFα induces a catabolic state in human adipose tissue which includes a loss of the stimulatory effect of insulin on glucose transport. These multiple actions of TNFα may contribute to the loss of adipose tissue observed during cachexia in man.

Key words

Cachexia glucose transport human adipocytes insulin resistance lipolysis tumour necrosis factor alpha 

Abbreviations

TNFα

Tumour necrosis factor alpha

LPL

lipoprotein lipase

HEPES

N-2-Hydroxyethylpiperazine-N-2-ethanesulfonic acid

MIX

1-Methy1-3-isobutylxanthine

BSA

bovine serum albumin

GPDH

glycerophosphate dehydrogenase

PBS

phosphate buffered saline

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • H. Hauner
    • 1
  • Th. Petruschke
    • 1
  • M. Russ
    • 1
  • K. Röhrig
    • 1
  • J. Eckel
    • 1
  1. 1.Diabetes Research InstituteHeinrich-Heine-UniversityDüsseldorfGermany
  2. 2.Diabetes Research InstituteHeinrich-Heine-University DüsseldorfDüsseldorfGermany

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