Inhibitor of DNA binding 2 is a small molecule-inducible modulator of peroxisome proliferator-activated receptor-γ expression and adipocyte differentiation
Inhibitor of DNA binding 2 is a small molecule-inducible modulator of peroxisome proliferator-activated receptor-γ expression and adipocyte differentiation
复制标题
DOI：
10.1210/me.2007-0454
复制
发表时间：
2008-09-01
影响因子：
--
通讯作者：
Tontonoz, Peter
中科院分区：
文献类型：
--
作者：
Park, Kye Won;Waki, Hironori;Tontonoz, Peter
我们以前确定了小分子骆驼蓬碱作为过氧化物酶体增殖物激活受体γ（PPAR γ）和脂肪细胞分化的调节剂。为了鉴定介导去氢骆驼蓬碱作用的信号通路，我们对3 T3-F442 A前脂肪细胞进行了转录谱分析。DNA结合抑制因子2（Inhibitor of DNA biding 2，Id 2）是一个能被骆驼蓬碱快速诱导的基因，但不能被过氧化物酶体增殖物激活受体γ激动剂诱导。Id 2也在用地塞米松、3-异丁基-1-甲基黄嘌呤和胰岛素处理的3 T3-L1前脂肪细胞中诱导，表明Id 2调节是脂肪形成程序的共同特征。Id 2在前脂肪细胞中的稳定过表达促进了PPAR γ的表达，并增强了形态分化和脂质积累。相反，小干扰RNA介导的Id 2敲低拮抗脂肪细胞分化。缺乏Id 2表达的小鼠表现出减少的肥胖，并且源自这些小鼠的胚胎成纤维细胞表现出减少的PPAR γ表达和减少的脂肪细胞分化能力。最后，Id 2表达在肥胖小鼠和人的脂肪组织中升高。这些结果概述了Id 2在调节PPAR γ表达和脂肪形成中的作用，并强调了脂肪形成小分子作为解剖脂肪细胞生物学的工具的实用性。
We previously identified the small molecule harmine as a regulator of peroxisome proliferator activated-receptor gamma(PPAR gamma) and adipocyte differentiation. In an effort to identify signaling pathways mediating harmine's effects, we performed transcriptional profiling of 3T3-F442A preadipocytes. Inhibitor of DNA biding 2 (Id2) was identified as a gene rapidly induced by harmine but not by PPAR gamma agonists. Id2 is also induced in 3T3-L1 preadipocytes treated with dexamethasone, 3-isobutyl-1-methylxanthine, and insulin, suggesting that Id2 regulation is a common feature of the adipogenic program. Stable overexpression of Id2 in preadipocytes promotes expression of PPAR gamma and enhances morphological differentiation and lipid accumulation. Conversely, small interfering RNA-mediated knockdown of Id2 antagonizes adipocyte differentiation. Mice lacking Id2 expression display reduced adiposity, and embryonic fibroblasts derived from these mice exhibit reduced PPAR gamma expression and a diminished capacity for adipocyte differentiation. Finally, Id2 expression is elevated in adipose tissues of obese mice and humans. These results outline a role for Id2 in the modulation of PPAR gamma expression and adipogenesis and underscore the utility of adipogenic small molecules as tools to dissect adipocyte biology.