Klein Johannes, Fasshauer Mathias, Klein Harald H, Benito Manuel, Kahn C Ronald
Department of Internal Medicine I, Medical University of Lübeck, Germany.
Bioessays. 2002 Apr;24(4):382-8. doi: 10.1002/bies.10058.
Adipose tissue has emerged as an important endocrine regulator of glucose metabolism and energy homeostasis. By virtue of the mitochondrial protein uncoupling protein-1 (UCP-1), brown fat additionally plays a unique role in thermoregulation. Interest has focused on this tissue not only as a target for pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue with leptin secretion and high insulin sensitivity. Most studies of adipocytes have been limited either to primary cell culture or to a small number of established cell lines. Recently, we have generated immortalized brown adipocyte cell lines from single newborn mice of different knockout mouse models. These cell lines retain the main characteristics of primary cells including UCP-1 expression. They display sensitive and diverse metabolic responses to insulin and adrenergic stimulation and have proven to be useful in the characterization of UCP regulation and the role of key insulin signaling elements for insulin action. Here, we outline common approaches to the generation of adipose tissue cell lines. Furthermore, we propose that the novel technique of generating brown adipocyte lines from a single newborn mouse will be instrumental in gaining further insight into the role of a broad range of signaling molecules in adipose tissue biology and in the pathogenesis of insulin resistance.
脂肪组织已成为葡萄糖代谢和能量稳态的重要内分泌调节因子。借助线粒体蛋白解偶联蛋白-1（UCP-1），棕色脂肪在体温调节中还发挥着独特作用。人们不仅将该组织视为肥胖和胰岛素抵抗药物治疗的靶点，还将其视为具有瘦素分泌和高胰岛素敏感性的内分泌组织。大多数对脂肪细胞的研究要么局限于原代细胞培养，要么局限于少数已建立的细胞系。最近，我们从不同基因敲除小鼠模型的新生小鼠个体中建立了永生化棕色脂肪细胞系。这些细胞系保留了原代细胞的主要特征，包括UCP-1表达。它们对胰岛素和肾上腺素能刺激表现出敏感且多样的代谢反应，并且已被证明有助于表征UCP调节以及关键胰岛素信号元件在胰岛素作用中的作用。在此，我们概述了生成脂肪组织细胞系的常见方法。此外，我们提出从新生小鼠个体中生成棕色脂肪细胞系的新技术将有助于进一步深入了解多种信号分子在脂肪组织生物学和胰岛素抵抗发病机制中的作用。
