Opposing effects of tumour necrosis factor α and hyperosmolarity on Na+/myo-inositol co-transporter mRNA levels and myo-inositol accumulation by 3T3-L1 adipocytes

Mark A. Yorek*, Joyce A. Dunlap, William L. Lowe

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Tumour necrosis factor α (TNF-α) regulates the transport of myo-inositol in 3T3-L1 adipocytes. Treating 3T3-L1 adipocytes with TNF-α decreases Na+/nyo-inositol co-transporter (SMIT) mRNA levels and myo-inositol accumulation in a concentration- and time-dependent manner. TNF-α decreases the V(max) for high-affinity myo-inositol transport with little change in the K'(m). Studies with actinomycin D suggest that RNA synthesis is required for the TNF-α-induced effect on SMIT mRNA levels. In contrast with the effect of TNF-α, hyperosmolarity increases SMIT mRNA levels and myo-inositol accumulation in 3T3-L1 adipocytes. Hyperosmolarity increases SMIT gene expression as evidenced by the inhibition of hyperosmotic induction of SMIT mRNA levels by actinomycin D, and of myo-inositol accumulation by actinomycin D and cycloheximide. TNF-α and osmotic stress have previously been shown to activate similar signal transduction pathways in mammalian cells. In 3T3-L1 adipocytes, both TNF-α and hyperosmolarity increase mitogen-activated protein kinase kinase pathway activity; however, with the possible exception of c-Jun N-terminal kinase, this pathway does not seem to regulate SMIT mRNA levels or myo-inositol accumulation. TNF-α activates nuclear factor κB (NF-κB) in 3T3-L1 adipocytes but, unlike the effect of TNF-α on cultured endothelial cells, NF-κB does not seem to contribute to the regulation by TNF-α of SMIT gene expression in 3T3-L1 adipocytes. Therefore other signal transduction pathways must be considered in the regulation by TNF-α of SMIT mRNA levels and activity. Thus TNF-α and hyperosmolarity have opposing effects on SMIT mRNA levels and activity in 3T3-L1 adipocytes. Because myo-inositol in the form of phosphoinositides is an important component of membranes and signal transduction pathways, the regulation of myo-inositol metabolism by TNF-α might represent another mechanism by which TNF-α regulates adipocyte function.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalBiochemical Journal
Volume336
Issue number2
DOIs
StatePublished - Dec 1 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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