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 -