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

Francis R. Weiner, Pamela J. Smith, Stanley Wertheimer, Charles 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 15 1991

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Stearoyl-CoA Desaturase
Coenzyme A Ligases
3T3-L1 Cells
Gene encoding
Gene Expression Regulation
Transcription
Adipocytes
Gene expression
Tumor Necrosis Factor-alpha
Genes
Modulation
Insulin
Metabolism
Enzymes
Fatty Acids
Cytokines
Messenger RNA
Lipoprotein Lipase
Transcriptional Activation
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

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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. / Weiner, Francis R.; Smith, Pamela J.; Wertheimer, Stanley; Rubin, Charles S.

In: Journal of Biological Chemistry, Vol. 266, No. 35, 15.12.1991, p. 23525-23528.

Research output: Contribution to journalArticle

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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.",
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