Regulation of gene expression by insulin and tumor necrosis factor α in 3T3-L1 cells: Modulation of the transcription of genes encoding acyl-CoA synthetase and stearoyl-CoA desaturase-1

F. R. Weiner, P. J. Smith, S. Wertheimer, C. S. Rubin

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Abstract

Insulin and tumor necrosis factor α (TNFα) produce potent and opposing physiological signals in adipocytes. However, genes that are co-regulated by the hormone and cytokine during and after adipocyte differentiation have not been characterized. Using 3T3-L1 cells, we have studied the regulation of the expression of genes encoding acyl-CoA synthetase (ACS), and stearoyl CoA desaturase-1 (SCD-1), two enzymes that play key roles in the metabolism of long chain fatty acids. Insulin is required for triggering the transcriptional activation of the ACS and SCD-1 genes at an early stage in adipocyte differentiation. In mature adipocytes insulin elicits a 4-fold increase in the rates of transcription of the two genes. However, when 3T3-L1 adipocytes are treated with TNFα the cytokine causes a 75-90% decrease in the levels of ACS and SCD-1 mRNAs. The decline in mRNA content is associated with similar decrements in the rates of transcription of the ACS and SCD-1 genes. Thus, the ACS and SCD-1 genes are subject to stimulation and counter-regulation (at the transcriptional level) by insulin and TNFα, respectively. The opposing effects of insulin and TNFα are observed in developing and terminally differentiated adipocytes. Unlike the ACS and SCD-1 genes, the genes that encode the lipogenic enzymes lipoprotein lipase and malic enzyme are not subject to counter-regulation by insulin and TNFα at the transcriptional level in 3T3-L1 adipocytes. These observations on the control of ACS and SCD-1 expression suggest possible mechanisms by which adipocytes can markedly adjust their capacity for long chain fatty acid metabolism in response to external stimuli.

Original languageEnglish (US)
Pages (from-to)23525-23528
Number of pages4
JournalJournal of Biological Chemistry
Volume266
Issue number35
StatePublished - Dec 1 1991

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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