Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia.
To investigate whether interleukin 6 (IL-6) might be a potential mediator of the depleted fat reserves observed in malignancy-associated cachexia, we measured lipoprotein lipase (LPL) activity in adipose tissue of mice after administration of IL-6 or tumor necrosis factor and in cultured adipocytes after addition of these cytokines. Injection of IL-6 i.p. reduced adipose tissue LPL activity by 53% within 4.5 to 5.5 h. Injection of tumor necrosis factor elevated serum IL-6 levels and reduced adipose tissue LPL activity by 70%. Both human and murine IL-6 reduced heparin-releasable LPL activity in 3T3-L1 adipocytes in a dose-dependent manner; half-maximal inhibition of LPL activity was achieved with 5000 hybridoma growth factor units/ml. Thus, IL-6 reduces adipose LPL activity and may contribute to the loss of body fat stores associated with some cases of cancer cachexia. Since tumor necrosis factor increases circulating IL-6, some of its effects may be mediated or potentiated by IL-6.
Greenberg
A S
AS
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes, Digestive and Kidney Disease, NIH, Bethesda, Maryland 20892.
Nordan
R P
RP
McIntosh
J
J
Calvo
J C
JC
Scow
R O
RO
Jablons
D
D
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology*; D000818:Animals; D002999:Clone Cells; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase