title: Hypoxia induces glucose uptake and metabolism of adipose‑derived stem cells.
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.
authors.affiliation: Department of Pharmaceutics and Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.
authors.forename: Hyoung Sook
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Pharmaceutics and Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutics and Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Sun
authors.affiliation: Translational Research Center, Inha University School of Medicine, Incheon 22332, Republic of Korea.
authors.forename: Sun U
authors.initials: SU
authors.lastname: Song
authors.affiliation: Department of Pharmacy, College of Pharmacy, Chung‑Ang University, Seoul 06974, Republic of Korea.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
authors.affiliation: Department of Pharmaceutics and Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Sung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006019:Glycolysis; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis; D020543:Proteome; D040901:Proteomics / Q000379:methods; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020543:Proteome; D019344:Lactic Acid; D005947:Glucose