Journal article
Regulation of glycolysis in brown adipocytes by HIF-1α.
- Basse AL Department of Biology, University of Copenhagen, Copenhagen, Denmark.
- Isidor MS Department of Biology, University of Copenhagen, Copenhagen, Denmark.
- Winther S Department of Biology, University of Copenhagen, Copenhagen, Denmark.
- Skjoldborg NB Department of Biology, University of Copenhagen, Copenhagen, Denmark.
- Murholm M Department of Biology, University of Copenhagen, Copenhagen, Denmark.
- Andersen ES Department of Biology, University of Copenhagen, Copenhagen, Denmark.
- Pedersen SB Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
- Wolfrum C Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
- Quistorff B Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Hansen JB Department of Biology, University of Copenhagen, Copenhagen, Denmark. jacob.hansen@bio.ku.dk.
- 2017-06-24
Published in:
- Scientific reports. - 2017
Adipocytes, Brown
Adrenergic beta-Agonists
Animals
Cells, Cultured
Cold Temperature
Gene Expression Regulation
Gene Expression Regulation, Enzymologic
Glucose
Glucose Transport Proteins, Facilitative
Glycolysis
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit
Male
Mice
Mitochondria
Models, Biological
Thermogenesis
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1038/s41598-017-04246-y
- PMID 28642579
- Persistent URL
- https://sonar.ch/global/documents/199385
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