Fu Mingui, Sun Tingwan, Bookout Angie L, Downes Michael, Yu Ruth T, Evans Ronald M, Mangelsdorf David J
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, Texas 75390-9050, USA.
Mol Endocrinol. 2005 Oct;19(10):2437-50. doi: 10.1210/me.2004-0539. Epub 2005 Jul 28.
The differentiation of a preadipocyte into a mature adipocyte represents a fundamental process in biology that requires a scripted program of transcriptional events leading to changes in gene expression. As part of our contribution to the Nuclear Receptor Signaling Atlas (NURSA), we used quantitative real-time PCR to profile the temporal expression of all 49 members of the mouse nuclear receptor superfamily at selected time points during differentiation of 3T3-L1 cells into mature, lipid-bearing adipocytes using two differentiation inducers [DMI (a cocktail of dexamethasone, 3-isobutyl-1-methylxanthine, and insulin) and rosiglitazone]. We also included a comparative analysis of nuclear receptor expression in mouse primary preadipocytes and mature adipocytes. In addition to confirming the expression of receptors known to be required for adipogenesis, this analysis revealed the existence of a tightly regulated transcriptional cascade that appeared in three distinct temporal phases. The first phase began within 4 h of adipogenic initiation with the transient, sequential expression of four previously uncharacterized receptors, followed by biphasic expression of a second subset, and ended with the sequential increase in a third receptor subset over a period of 2 wk after initiation. The discovery that these receptors may serve as adipogenic biomarkers and as potential therapeutic targets in adipose-related diseases highlights the utility of quantitative expression profiling as a method for directing mechanism-based approaches to study complex regulatory pathways.
前脂肪细胞分化为成熟脂肪细胞是生物学中的一个基本过程，这需要一个程序化的转录事件来导致基因表达的变化。作为我们对核受体信号图谱（NURSA）贡献的一部分，我们使用定量实时PCR，在3T3-L1细胞利用两种分化诱导剂[DMI（地塞米松、3-异丁基-1-甲基黄嘌呤和胰岛素的混合物）和罗格列酮]分化为成熟的含脂脂肪细胞的选定时间点，对小鼠核受体超家族的所有49个成员的时间表达进行了分析。我们还对小鼠原代前脂肪细胞和成熟脂肪细胞中的核受体表达进行了比较分析。除了证实已知脂肪生成所需受体的表达外，该分析还揭示了存在一个严格调控的转录级联反应，该反应出现在三个不同的时间阶段。第一阶段在脂肪生成开始后4小时内开始，四个先前未被鉴定的受体瞬时、顺序表达，随后第二组受体双相表达，并在开始后2周内第三组受体顺序增加而结束。这些受体可能作为脂肪生成生物标志物以及脂肪相关疾病潜在治疗靶点的发现，凸显了定量表达谱作为一种指导基于机制的方法来研究复杂调控途径的方法的实用性。
