Regulation of glycolysis in brown adipocytes by HIF-1α
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Regulation of glycolysis in brown adipocytes by HIF-1α. / Basse, Astrid Linde; Isidor, Marie Sophie; Winther, Sally; Skjoldborg, Nina B.; Murholm, Maria; Andersen, Elise S.; Pedersen, Steen B.; Wolfrum, Christian; Quistorff, Bjørn; Hansen, Jacob B.
In: Scientific Reports, Vol. 7, 4052, 22.06.2017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Regulation of glycolysis in brown adipocytes by HIF-1α
AU - Basse, Astrid Linde
AU - Isidor, Marie Sophie
AU - Winther, Sally
AU - Skjoldborg, Nina B.
AU - Murholm, Maria
AU - Andersen, Elise S.
AU - Pedersen, Steen B.
AU - Wolfrum, Christian
AU - Quistorff, Bjørn
AU - Hansen, Jacob B.
PY - 2017/6/22
Y1 - 2017/6/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021109721&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-04246-y
DO - 10.1038/s41598-017-04246-y
M3 - Journal article
C2 - 28642579
AN - SCOPUS:85021109721
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 4052
ER -
ID: 181383244