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Steen Bønløkke Pedersen

Regulation of glycolysis in brown adipocytes by HIF-1α

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DOI

  • Astrid L Basse, j Department of Biomedical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • ,
  • Marie S Isidor, j Department of Biomedical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • ,
  • Sally Winther, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
  • ,
  • Nina B Skjoldborg, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
  • ,
  • Maria Murholm, j Department of Biomedical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • ,
  • Elise S Andersen, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
  • ,
  • Steen B Pedersen
  • Christian Wolfrum, Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
  • ,
  • Bjørn Quistorff, j Department of Biomedical Sciences , University of Copenhagen , Copenhagen , Denmark.
  • ,
  • Jacob B Hansen, Department of Biology, University of Copenhagen, Copenhagen, Denmark. jacob.hansen@bio.ku.dk.

Brown adipose tissue takes up large amounts of glucose during cold exposure in mice and humans. Here we report an induction of glucose transporter 1 expression and increased expression of several glycolytic enzymes in brown adipose tissue from cold-exposed mice. Accordingly, these genes were also induced after β-adrenergic activation of cultured brown adipocytes, concomitant with accumulation of hypoxia inducible factor-1α (HIF-1α) protein levels. HIF-1α accumulation was dependent on uncoupling protein 1 and generation of mitochondrial reactive oxygen species. Expression of key glycolytic enzymes was reduced after knockdown of HIF-1α in mature brown adipocytes. Glucose consumption, lactate export and glycolytic capacity were reduced in brown adipocytes depleted of Hif-1α. Finally, we observed a decreased β-adrenergically induced oxygen consumption in Hif-1α knockdown adipocytes cultured in medium with glucose as the only exogenously added fuel. These data suggest that HIF-1α-dependent regulation of glycolysis is necessary for maximum glucose metabolism in brown adipocytes.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind7
Nummer1
Sider (fra-til)4052
ISSN2045-2322
DOI
StatusUdgivet - 22 jun. 2017

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