Recombinant human tumor necrosis factor does not inhibit lipoprotein lipase in primary cultures of isolated human adipocytes.
Previous studies have demonstrated that cachectin/tumor necrosis factor (TNF) inhibits lipoprotein lipase (LPL) activity in cultures of 3T3-L1 cells. To determine whether TNF also inhibits LPL in human adipocytes, primary cultures of isolated human adipocytes were exposed to a spectrum of concentrations of recombinant human TNF. TNF concentrations up to 1000 pM had no effect on either LPL activity or LPL immunoreactive mass in the human adipocytes. Specific binding of 125I-labeled TNF was demonstrated in human adipocytes, and a TNF concentration of 100 pM competed for approximately 50% of the 125I-labeled TNF binding sites. In contrast, the same TNF in the same concentrations progressively inhibited LPL activity and immunoreactive mass in 3T3-L1 cells. Thus, human adipocytes respond to TNF in a different manner than 3T3-L1 cells. TNF may not cause the cachexia of cancer or chronic infection by directly inhibiting LPL in adipose tissue.
Kern
P A
PA
Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles 90048.
D000273:Adipose Tissue / Q000201:enzymology*; D002478:Cells, Cultured; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D008071:Lipoprotein Lipase