title: Hypoxia induces a HIF-1α dependent signaling cascade to make a complex metabolic switch in SGBS-adipocytes.
abstract: To elucidate the complex impact of hypoxia on adipose tissue, resulting in biased metabolism, insulin resistance and finally diabetes we used mature adipocytes derived from a Simpson-Golabi-Behmel syndrome patient for microarray analysis. We found a significantly increased transcription rate of genes involved in glycolysis and a striking association between the pattern of upregulated genes and disease biomarkers for diabetes mellitus and insulin resistance. Although their upregulation turned out to be HIF-1α-dependent, we identified further transcription factors mainly AP-1 components to play also an important role in hypoxia response. Analyzing the regulatory network of mentioned transcription factors and glycolysis targets we revealed a clear hint for directing glycolysis to glutathione and glycogen synthesis. This metabolic switch in adipocytes enables the cell to prevent oxidative damage in the short term but might induce lipogenesis and establish systemic metabolic disorders in the long run.
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leiherer
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Geiger
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors.forename: Axel
authors.initials: A
authors.lastname: Muendlein
authors.affiliation: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Drexel University College of Medicine, Philadelphia, USA. Electronic address: vivit@lkhf.at.
authors.forename: Heinz
authors.initials: H
authors.lastname: Drexel
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005877:Gigantism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000096:biosynthesis; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D025941:Protein Interaction Mapping; D015398:Signal Transduction / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018808:Transcription Factor AP-1; D006003:Glycogen; D005978:Glutathione
keywords: Adipocytes; Gene expression profiling; Gene ontology; HIF-1; Hypoxia; SGBS