Hypoxia induces glucose uptake and metabolism of adipose‑derived stem cells

Park,Hyoung Sook; Kim,Ji Hye; Sun,Bo Kyung; Song,Sun U.; Suh,Wonhee; Sung,Jong‑Hyuk

doi:10.3892/mmr.2016.5796

Hypoxia induces glucose uptake and metabolism of adipose‑derived stem cells

Authors:
- Hyoung Sook Park
- Ji Hye Kim
- Bo Kyung Sun
- Sun U. Song
- Wonhee Suh
- Jong‑Hyuk Sung
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Affiliations: Department of Pharmaceutics and Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea, Translational Research Center, Inha University School of Medicine, Incheon 22332, Republic of Korea, Department of Pharmacy, College of Pharmacy, Chung‑Ang University, Seoul 06974, Republic of Korea
Published online on: October 5, 2016 https://doi.org/10.3892/mmr.2016.5796
Pages: 4706-4714

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Abstract

It has previously been demonstrated that hypoxia has diverse stimulatory effects on adipose‑derived stem cells (ASCs), however, metabolic responses under hypoxia remain to be elucidated. Thus, the present study aimed to investigate the glucose uptake and metabolism of ASCs under hypoxic conditions, and to identify the underlying molecular mechanisms. ASCs were cultured in 1% oxygen, and experiments were conducted in vitro. As determined by proteomic analysis and western blotting, GAPDH and enolase 1 (ENO1) expression were upregulated under hypoxia. In addition, lactate production was significantly increased, and mRNA levels of glycolytic enzymes, including GAPDH, ENO1, hexokinase 2 (HK2), and lactate dehydrogenase α (LDHα) were upregulated. Hypoxia‑inducible factor 1‑α (HIF‑1α) expression was increased as demonstrated by western blotting, and a pharmacological inhibitor of HIF‑1α significantly attenuated hypoxia‑induced lactate production and expression of glycolytic enzymes. It was also observed that hypoxia significantly increased glucose uptake in ASCs, and glucose transporter (GLUT)1 and GLUT3 expression were upregulated under hypoxia. Pharmacological inhibition of the HIF‑1α signaling pathways also attenuated hypoxia‑induced GLUT1 and GLUT3 expression. These results collectively indicate that hypoxia increases glucose uptake via GLUT1 and GLUT3 upregulation, and induces lactate production of ASCs via GAPDH, ENO1, HK2, and LDHα. Furthermore, HIF‑1α is involved in glucose uptake and metabolism of ASCs.

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