Differential regulation by tumor necrosis factor-alpha of beta1-, beta2-, and beta3-adrenoreceptor gene expression in 3T3-F442A adipocytes.
Modulation of beta-adrenoreceptor expression by tumor necrosis factor-alpha (TNF-alpha) was investigated in murine 3T3-F442A adipocytes. TNF-alpha treatment of mature adipocytes decreased beta3-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-alpha. beta1-Adrenoreceptor mRNA abundance was slightly decreased by TNF-alpha treatment, while beta2-adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (-)-[125I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-alpha induced a 2-fold decrease in beta3-adrenoreceptor number, a nonsignificant reduction in beta1-subtype population, and a approximately 4.5-fold increase in beta2-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-alpha increased both beta2-adrenoreceptor gene transcription and beta2-adrenoreceptor mRNA half-life, while beta1- and beta3-adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-alpha of the three beta-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.
Hadri
K E
KE
INSERM Unité 282, Hôpital Henri Mondor, 94010 Créteil, France.
Courtalon
A
A
Gauthereau
X
X
Chambaut-Guérin
A M
AM
Pairault
J
J
Fève
B
B
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha