Hypoxia induces a HIF-1α dependent signaling cascade to make a complex metabolic switch in SGBS-adipocytes

Andreas Leiherer; Kathrin Geiger; Axel Muendlein; Heinz Drexel

doi:10.1016/j.mce.2013.11.009

Hypoxia induces a HIF-1α dependent signaling cascade to make a complex metabolic switch in SGBS-adipocytes

Mol Cell Endocrinol. 2014 Mar 5;383(1-2):21-31. doi: 10.1016/j.mce.2013.11.009. Epub 2013 Nov 22.

Authors

Andreas Leiherer¹, Kathrin Geiger², Axel Muendlein², Heinz Drexel³

Affiliations

¹ Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Medical Central Laboratories, Feldkirch, Austria.
² Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
³ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / metabolism*
Adipocytes / pathology
Adipogenesis
Arrhythmias, Cardiac / genetics
Arrhythmias, Cardiac / metabolism*
Arrhythmias, Cardiac / pathology
Biomarkers / metabolism
Cell Hypoxia / genetics
Gene Expression Profiling
Gene Expression Regulation
Genetic Diseases, X-Linked / genetics
Genetic Diseases, X-Linked / metabolism*
Genetic Diseases, X-Linked / pathology
Gigantism / genetics
Gigantism / metabolism*
Gigantism / pathology
Glutathione / biosynthesis
Glycogen / biosynthesis
Glycolysis
Heart Defects, Congenital / genetics
Heart Defects, Congenital / metabolism*
Heart Defects, Congenital / pathology
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Insulin Resistance
Intellectual Disability / genetics
Intellectual Disability / metabolism*
Intellectual Disability / pathology
Oligonucleotide Array Sequence Analysis
Protein Interaction Mapping
Signal Transduction / genetics*
Transcription Factor AP-1 / genetics*
Transcription Factor AP-1 / metabolism
Transcription, Genetic

Substances

Biomarkers
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Transcription Factor AP-1
Glycogen
Glutathione

Supplementary concepts

Simpson-Golabi-Behmel syndrome