title: A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes.
abstract: The effect of hypoxia on global gene expression in human adipocytes has been examined using DNA microarrays. Adipocytes (Zen-Bio, day 12 post-differentiation) were exposed to hypoxia (1% O(2)) or 'normoxia' (21% O(2)) for 24 h and extracted RNA probed with Agilent arrays containing 41,152 probes. A total of 1346 probes were differentially expressed (>2.0-fold change, P < 0.01) in response to hypoxia; 650 genes were up-regulated (including LEP, IL6, VEGF, ANGPTL4) and 650 down-regulated (including ADIPOQ, UCP2). Major genes not previously identified as hypoxia-sensitive in adipocytes include AQP3, FABP3, FABP5 and PPARGC1A. Ingenuity analysis indicated that several pathways and functions were modulated by hypoxia, including glucose utilization, lipid oxidation and cell death. Network analysis indicated a down-regulation of p38/MAPK and PGC-1α signalling in the adipocytes. It is concluded that hypoxia has extensive effects on human adipocyte gene expression, consistent with low O(2) tension underlying adipose tissue dysfunction in obesity.
authors.affiliation: Unilever R&D Discover, Colworth Park, Bedfordshire MK44 1LQ, United Kingdom.
authors.forename: Dawn
authors.initials: D
authors.lastname: Mazzatti
authors.forename: Fei-Ling
authors.initials: FL
authors.lastname: Lim
authors.forename: Adrian
authors.initials: A
authors.lastname: O'Hara
authors.forename: I Stuart
authors.initials: IS
authors.lastname: Wood
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks; D005947:Glucose / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen