Hypoxia induces apelin expression in human adipocytes.

Adipokines play a central role in the development of diseases associated with insulin resistance and obesity. Hypoxia in adipose tissue leads to a dysregulation of the expression of adipokines. The effect of hypoxia on the more recently identified adipokine apelin in human adipocytes is unclear. Therefore, we aimed at investigating the role of hypoxia on the expression of the adipokine apelin. Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured under hypoxic conditions for varying time periods. A modular incubator chamber was used to create a hypoxic tissue culture environment (defined as 1% O(2), 94% N, and 5% CO(2)). In addition, hypoxic conditions were mimicked by using CoCl(2). The effect of hypoxia on the expression of the investigated adipokines was measured by real-time PCR and the secretion of apelin was quantified by ELISA. Induction of hypoxia significantly induced mRNA expression of leptin and apelin in differentiated SGBS adipocytes compared with the normoxic control condition. Expression of adiponectin was significantly decreased by hypoxia. In addition, the amount of secreted apelin protein in response to hypoxia was elevated compared to untreated cells. Furthermore, we could demonstrate that the observed hypoxia-induced induction of apelin mRNA expression is in the first phase dependent on HIF-1α. In our study, we could demonstrate for the first time that apelin expression and secretion by human adipocytes are strongly induced under hypoxic conditions and that the early response on hypoxia with apelin induction is dependent on HIF-1α.

Geiger K ，Muendlein A ，Stark N ，Saely CH ，Wabitsch M ，Fraunberger P ，Drexel H ... -  《-》

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

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.

Leiherer A ，Geiger K ，Muendlein A ，Drexel H ... -  《-》

Human growth hormone receptor (GHR) expression in obesity: II. Regulation of the human GHR gene by obesity-related factors.

Erman A ，Wabitsch M ，Goodyer CG 《-》

Simpson-Golabi-Behmel syndrome human adipocytes reveal a changing phenotype throughout differentiation.

Montanari T ，Colitti M 《-》

Resveratrol metabolites modify adipokine expression and secretion in 3T3-L1 pre-adipocytes and mature adipocytes.

Eseberri I ，Lasa A ，Churruca I ，Portillo MP ... -  《PLoS One》