Paul-Langerhans-Group, Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
Mol Cell Endocrinol. 2012 Oct 15;362(1-2):194-201. doi: 10.1016/j.mce.2012.06.010. Epub 2012 Jun 28.
It is widely accepted that obesity is a major risk factor for the development of atherosclerosis. In this context, adipose tissue produces a variety of adipokines and releases free fatty acids, contributing to a chronic-low grade inflammation state implicated in vascular complications. In this study, we investigated the role of adipokines, oleic acid (OA), palmitic acid (PA), and the combinations on activation of NF-κB target genes in human vascular smooth muscle cells (SMC) to assess the hypothesis of synergistic interactions between these molecules. Adipocyte-conditioned medium (CM), generated from human adipocytes, in combination with low concentrations of OA, but not PA, induces SMC proliferation and activation of the transcription factor NF-κB in a synergistic way. Combined treatment of CM and OA further regulates a set of downstream NF-κB target genes including angiopoietin-1, activin A, and MMP-1, all critically involved in SMC dysfunction. This suggests that the lipotoxic potential of fatty acids is substantially enhanced by the presence of adipocyte-derived factors.
人们普遍认为肥胖是动脉粥样硬化发展的一个主要危险因素。在这种情况下，脂肪组织会产生多种脂肪因子，并释放游离脂肪酸，导致慢性低度炎症状态，从而引发血管并发症。在这项研究中，我们研究了脂肪因子、油酸（OA）、棕榈酸（PA）及其组合对人血管平滑肌细胞（SMC）中 NF-κB 靶基因激活的作用，以评估这些分子之间协同作用的假设。由人脂肪细胞生成的脂肪细胞条件培养基（CM）与低浓度的 OA 而非 PA 联合，以协同方式诱导 SMC 增殖和转录因子 NF-κB 的激活。CM 和 OA 的联合处理进一步调节了一组下游 NF-κB 靶基因，包括血管生成素 1、激活素 A 和 MMP-1，所有这些都与 SMC 功能障碍密切相关。这表明脂肪酸的脂毒性潜能因脂肪细胞衍生因子的存在而大大增强。
