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Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes*

K. E. Hadri,A. Courtalon,X. Gauthereau,A. Chambaut-Guérin,J. Pairault,B. Fève

Published 1997 in Journal of Biological Chemistry

ABSTRACT

Modulation of β-adrenoreceptor expression by tumor necrosis factor-α (TNF-α) was investigated in murine 3T3-F442A adipocytes. TNF-α treatment of mature adipocytes decreased β3-adrenoreceptor mRNA content in a time- and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pm TNF-α. β1-Adrenoreceptor mRNA abundance was slightly decreased by TNF-α treatment, while β2-adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (−)-[125I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-α induced a 2-fold decrease in β3-adrenoreceptor number, a nonsignificant reduction in β1-subtype population, and a ∼4.5-fold increase in β2-adrenoreceptor density. This correlated with a lower EC50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-α increased both β2-adrenoreceptor gene transcription and β2-adrenoreceptor mRNA half-life, while β1- and β3-adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-α of the three β-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.

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