Chemical genetic identification of the histamine H1 receptor as a stimulator of insulin-induced adipogenesis
Chemical genetic identification of the histamine H1 receptor as a stimulator of insulin-induced adipogenesis
复制标题
DOI：
10.1016/j.chembiol.2004.04.017
复制
发表时间：
2004-07-01
影响因子：
--
通讯作者：
Uesugi, M
中科院分区：
文献类型：
--
作者：
Kawazoe, Y;Tanaka, S;Uesugi, M
大量具有不同生物学效应的生物活性化合物可用作探针，以阐明影响特定细胞过程的新生物学机制。在这里，我们分析了880种众所周知的小分子生物活性物质或药物对3 T3-L1成纤维细胞（脂肪细胞分化的细胞培养模型）胰岛素诱导的脂肪形成的影响。我们的筛选鉴定了86种化合物作为3 T3-L1细胞脂肪形成分化的调节剂。他们的化学和药理学信息的检查显示，具有不同化学支架的抗组胺药物抑制分化。组胺H1受体在3 T3-L1细胞中表达，其被小干扰RNA（small interfering RNA，siRNA）敲低会损害胰岛素诱导的成脂分化。组胺受体和组胺样生物胺可能在胰岛素诱导脂肪形成中起作用。
A large collection of bioactive compounds with diverse biological effects can be used as probes to elucidate new biological mechanisms that influence a particular cellular process. Here we analyze the effects of 880 well-known small-molecule bioactives or drugs on the insulin-induced adipogenesis of 3T3-L1 fibroblasts, a cell-culture model of fat cell differentiation. Our screen identified 86 compounds as modulators of the adipogenic differentiation of 3T3-L1 cells. Examination of their chemical and pharmacological information revealed that antihistamine drugs with distinct chemical scaffolds inhibit differentiation. Histamine H1 receptor is expressed in 3T3-L1 cells, and its knockdown by small interfering RNA impaired the insulin-induced adipogenic differentiation. Histamine receptors and histamine-like biogenic amines may play a role in inducing adipogenesis in response to insulin.