Vorarlberg Institute for Vascular Investigation and Treatment, Feldkirch, Austria.
Horm Metab Res. 2011 Jun;43(6):380-5. doi: 10.1055/s-0031-1273767. Epub 2011 Mar 29.
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.
脂肪细胞因子在与胰岛素抵抗和肥胖相关的疾病发展中起着核心作用。脂肪组织缺氧会导致脂肪细胞因子表达失调。缺氧对新近发现的脂肪细胞因子脂联素在人脂肪细胞中的影响尚不清楚。因此，我们旨在研究缺氧对脂肪细胞因子脂联素表达的影响。分化的人类 Simpson-Golabi-Behmel 综合征 (SGBS) 脂肪细胞在缺氧条件下培养不同时间。使用模块化孵育箱室来创建缺氧组织培养环境（定义为 1% O2、94% N 和 5% CO2）。此外，通过使用 CoCl2 模拟缺氧条件。通过实时 PCR 测量缺氧对所研究脂肪细胞因子表达的影响，并通过 ELISA 定量测定脂联素的分泌。与正常氧条件相比，缺氧显著诱导分化的 SGBS 脂肪细胞中瘦素和脂联素的 mRNA 表达。缺氧显著降低脂联素的表达。此外，与未经处理的细胞相比，对缺氧的反应中分泌的脂联素蛋白的量增加。此外，我们还能够证明观察到的缺氧诱导的脂联素 mRNA 表达的第一阶段依赖于 HIF-1α。在我们的研究中，我们首次证明了人脂肪细胞中的脂联素表达和分泌在缺氧条件下强烈诱导，并且脂联素诱导的早期反应依赖于 HIF-1α。
