Norepinephrine but not hypoxia stimulates HIF-1alpha gene expression in brown adipocytes.
The cellular response to hypoxic stress is mainly mediated via activation of the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha). In the present study, the sympathetically controlled brown adipose tissue was used to investigate the effect of norepinephrine on HIF-1alpha gene expression. Norepinephrine increased HIF-1alpha mRNA levels in cultured brown adipocytes, whereas the hypoxia-mimic cobalt was without effect. Cold exposure of mice increased HIF-1alpha gene expression in brown adipose tissue. In UCP1-ablated mice, which are incapable of inducing thermogenic oxygen consumption in brown adipose tissue, cold exposure generated a significantly higher elevation of HIF-1alpha mRNA levels than in wild-type. These results demonstrate that cold-induced HIF-1alpha gene expression is independent of thermogenic oxygen consumption leading to hypoxia, but is consistent with a norepinephrine regulation of HIF-1alpha gene expression. Thus, by elevating HIF-1alpha gene expression, norepinephrine may mediate an increased potential to respond to hypoxia in brown adipose tissue and possibly in other tissues.
Nikami
Hideki
H
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Nedergaard
Jan
J
Fredriksson
J Magnus
JM
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003080:Cold Temperature; D005260:Female; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors; D009638:Norepinephrine