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

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.

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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Author information

Correspondence to H. Hauner or Th. Petruschke or M. Russ or K. Röhrig or J. Eckel.

Additional information

The main results of this study have been presented in abstract form at the Keystone-Symposium “The Adipose Cell”, January 1994, Park City, Utah, USA

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Hauner, H., Petruschke, T., Russ, M. et al. Effects of tumour necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologia 38, 764–771 (1995). https://doi.org/10.1007/s001250050350

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Key words

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