Effects of Hyperinsulinemia on Lipolytic Function of Three-Dimensional Adipocyte/Endothelial Co-Cultures
Effects of Hyperinsulinemia on Lipolytic Function of Three-Dimensional Adipocyte/Endothelial Co-Cultures
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DOI：
10.1089/ten.tec.2009.0760
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发表时间：
2010-10-01
影响因子：
3
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Choi, Jennifer H.;Gimble, Jeffrey M.;Kaplan, David L.
2 型糖尿病和肥胖症发病率的增加促使需要开发生理相关的脂肪组织模型，以对正常和患病脂肪功能进行对照研究。胰岛素抵抗是 2 型糖尿病和肥胖症的特征，通常先出现高胰岛素血症。我们在这里提出了一种三维（3D）共培养脂肪组织模型来研究高胰岛素暴露的影响，这使得研究生理细胞对高胰岛素血症的反应成为可能。最初进行二维脂肪细胞研究是为了建立基线控制，其中确定胰岛素水平。随后将脂肪细胞和内皮细胞在正常或高胰岛素浓度下在 3D 多孔丝素蛋白支架上共培养，并评估它们在脂肪生成和脂肪分解方面的生理反应。与正常胰岛素条件相比，高胰岛素水平会刺激甘油三酯积累的增加和脂肪分解水平的降低。相反，脂肪细胞单一培养物在胰岛素水平之间没有表现出任何差异。该 3D 系统能够在共培养中引发对高胰岛素血症的生理反应，这是脂肪组织工程向前迈出的重要一步。生理相关 3D 体外脂肪组织模型的开发为疾病机制研究以及评估治疗方法带来了希望。
The increased incidence of both type 2 diabetes mellitus and obesity has prompted the need to develop physiologically relevant adipose tissue models for controlled study of both normal and diseased adipose functions. Insulin resistance, characteristic of both type 2 diabetes mellitus and obesity, is often preceded by hyperinsulinemia. We propose here a three-dimensional (3D) co-culture adipose tissue model to study the effects of high insulin exposure, which enabled the study of physiological cell responses to hyperinsulinemic conditions. Two-dimensional adipocyte studies were initially conducted to establish a baseline control in which insulin levels were established. Adipocytes and endothelial cells were subsequently co-cultured on 3D porous silk fibroin scaffolds in normal or high insulin concentrations, and their physiological responses were assessed with respect to lipogenesis and lipolysis. High insulin levels stimulated both an increase in triglyceride accumulation and a decrease in lipolysis levels compared to that of normal insulin conditions. In contrast, adipocyte monocultures did not exhibit any differences between insulin levels. The ability of this 3D system to elicit physiological responses to hyperinsulinemia in co-culture serves as a significant step forward in adipose tissue engineering. The development of physiologically relevant 3D in vitro adipose tissue models presents promise for the study of disease mechanisms as well as in assessing therapeutic treatments.