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.
Keywords:
Adipocytes; Gene expression profiling; Gene ontology; HIF-1; Hypoxia; SGBS.
Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / metabolism*
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Adipocytes / pathology
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Adipogenesis
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Arrhythmias, Cardiac / genetics
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Arrhythmias, Cardiac / metabolism*
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Arrhythmias, Cardiac / pathology
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Biomarkers / metabolism
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Cell Hypoxia / genetics
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Gene Expression Profiling
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Gene Expression Regulation
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Genetic Diseases, X-Linked / genetics
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Genetic Diseases, X-Linked / metabolism*
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Genetic Diseases, X-Linked / pathology
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Gigantism / genetics
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Gigantism / metabolism*
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Gigantism / pathology
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Glutathione / biosynthesis
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Glycogen / biosynthesis
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Glycolysis
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Heart Defects, Congenital / genetics
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Heart Defects, Congenital / metabolism*
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Heart Defects, Congenital / pathology
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Insulin Resistance
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Intellectual Disability / genetics
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Intellectual Disability / metabolism*
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Intellectual Disability / pathology
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Oligonucleotide Array Sequence Analysis
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Protein Interaction Mapping
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Signal Transduction / genetics*
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Transcription Factor AP-1 / genetics*
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Transcription Factor AP-1 / metabolism
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Transcription, Genetic
Substances
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Biomarkers
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Transcription Factor AP-1
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Glycogen
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Glutathione
Supplementary concepts
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Simpson-Golabi-Behmel syndrome