Analysis of transcription factor network underlying 3T3-L1 adipocyte differentiation.
Analysis of transcription factor network underlying 3T3-L1 adipocyte differentiation.
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DOI：
10.1371/journal.pone.0100177
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Jayaraman A
中科院分区：
文献类型：
--
作者：
Choi K;Ghaddar B;Moya C;Shi H;Sridharan GV;Lee K;Jayaraman A
脂肪细胞中的脂质积累反映了导致酯化脂质（主要是甘油三酯）形成和分解的酶途径之间的平衡。 This balance is extremely important, as both high and low lipid levels in adipocytes can have deleterious consequences.负责脂质合成和分解（分别为脂肪生成和脂肪分解）的酶通过多种转录因子 (TF) 的协调作用进行调节。在这项研究中，我们检查了几个关键转录因子 (TF) - PPARγ、C/EBPβ、CREB、NFAT、FoxO1 和 SREBP-1c - 在脂肪形成分化（第 1 周）和随后的脂质积累过程中的动态。使用构建为在 TF 与其 DNA 结合元件结合后分泌高斯荧光素酶的 3T3-L1 报告细胞系，对诱导脂肪分化后不同时间的这些 TF 的激活谱进行定量。还使用逻辑门和常微分方程的组合对 TF 的动力学进行建模，其中逻辑门用于探索 PPARγ、C/EBPβ 和 SREBP-1c 激活输入的不同组合。实验概况和模型模拟的比较表明，SREBP-1c 可以由胰岛素或 PPARγ 独立激活，而 PPARγ 激活需要 C/EBPβ 以及假定的配体。参数估计和敏感性分析表明，与胰岛素对 SREBP-1c 的激活相比，PPARγ 对 SREBP-1c 的反馈激活可以忽略不计。 On the other hand, the production of an activating ligand could quantitatively contribute to a sustained elevation in PPARγ activity.
Lipid accumulation in adipocytes reflects a balance between enzymatic pathways leading to the formation and breakdown of esterified lipids, primarily triglycerides. This balance is extremely important, as both high and low lipid levels in adipocytes can have deleterious consequences. The enzymes responsible for lipid synthesis and breakdown (lipogenesis and lipolysis, respectively) are regulated through the coordinated actions of several transcription factors (TFs). In this study, we examined the dynamics of several key transcription factors (TFs) - PPARγ, C/EBPβ, CREB, NFAT, FoxO1, and SREBP-1c - during adipogenic differentiation (week 1) and ensuing lipid accumulation. The activation profiles of these TFs at different times following induction of adipogenic differentiation were quantified using 3T3-L1 reporter cell lines constructed to secrete the Gaussia luciferase enzyme upon binding of a TF to its DNA binding element. The dynamics of the TFs was also modeled using a combination of logical gates and ordinary differential equations, where the logical gates were used to explore different combinations of activating inputs for PPARγ, C/EBPβ, and SREBP-1c. Comparisons of the experimental profiles and model simulations suggest that SREBP-1c could be independently activated by either insulin or PPARγ, whereas PPARγ activation required both C/EBPβ as well as a putative ligand. Parameter estimation and sensitivity analysis indicate that feedback activation of SREBP-1c by PPARγ is negligible in comparison to activation of SREBP-1c by insulin. On the other hand, the production of an activating ligand could quantitatively contribute to a sustained elevation in PPARγ activity.
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影响因子：
4
作者：
Chan, Chi-Ping;Mak, To-Yuen;Jin, Dong-Yan
通讯作者：
Jin, Dong-Yan
影响因子：
4.3
作者：
Aldridge BB;Saez-Rodriguez J;Muhlich JL;Sorger PK;Lauffenburger DA
通讯作者：
Lauffenburger DA
DOI：
10.1006/bbrc.1997.7627
发表时间：
1997-11-07
影响因子：
3.1
作者：
Clarke, SL;Robinson, CE;Gimble, JM
通讯作者：
Gimble, JM
影响因子：
10.5
作者：
Kim, JB;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
--
作者：
Kraeutler, Matthew J.;Soltis, Anthony R.;Saucerman, Jeffrey J.
通讯作者：
Saucerman, Jeffrey J.