Med25 Limits Master Regulators That Govern Adipogenesis.
Med25 Limits Master Regulators That Govern Adipogenesis.
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DOI：
10.3390/ijms24076155
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发表时间：
2023-03-24
影响因子：
5.6
通讯作者：
Choi, Jason C. C.
中科院分区：
文献类型：
--
作者：
Saunders, Jasmine;Sikder, Kunal;Phillips, Elizabeth;Ishwar, Anurag;Mothy, David;Margulies, Kenneth B. B.;Choi, Jason C. C.
中介25 （Med25）是中介复合体的成员，将转录因子的信号传递给RNA聚合酶II机制。多种转录因子，特别是那些参与脂质代谢的转录因子，利用中介复合物，但Med25如何参与这一背景尚不清楚。我们之前在一种新的细胞类型特异性LMNA心肌病模型的成人心肌细胞（CMs）的翻译组筛选中发现了Med25。在这项研究中，我们发现Med25的上调与心肌脂质积累是一致的。为了确定Med25在脂质积累中的作用，我们利用ipsc衍生的和新生儿CMs在体外通过消耗层粘胶蛋白A和C（层粘胶蛋白A/C）来概括体内表型。尽管纤层蛋白A/C耗竭引起脂质积累，但这种影响似乎是由依赖于CM发育状态的不同机制介导的。为了直接研究Med25在脂质积累中的作用，我们在Med25沉默的3T3-L1前脂肪细胞中诱导脂肪形成，并检测到脂质积累的增强。对驱动脂肪形成的相关介质的评估显示，Med25沉默可超诱导C/EBPα和PPARγ。我们的研究结果表明，Med25通过抑制控制脂肪形成的主要调节因子的水平来限制脂肪形成的潜力。此外，我们警告使用早期发育阶段的心肌细胞来模拟成人阶段的细胞，特别是为了解剖由LMNA突变引起的代谢扰动。
Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context is unclear. We previously identified Med25 in a translatome screen of adult cardiomyocytes (CMs) in a novel cell type-specific model of LMNA cardiomyopathy. In this study, we show that Med25 upregulation is coincident with myocardial lipid accumulation. To ascertain the role of Med25 in lipid accumulation, we utilized iPSC-derived and neonatal CMs to recapitulate the in vivo phenotype by depleting lamins A and C (lamin A/C) in vitro. Although lamin A/C depletion elicits lipid accumulation, this effect appears to be mediated by divergent mechanisms dependent on the CM developmental state. To directly investigate Med25 in lipid accumulation, we induced adipogenesis in Med25-silenced 3T3-L1 preadipocytes and detected enhanced lipid accumulation. Assessment of pertinent mediators driving adipogenesis revealed that C/EBPα and PPARγ are super-induced by Med25 silencing. Our results indicate that Med25 limits adipogenic potential by suppressing the levels of master regulators that govern adipogenesis. Furthermore, we caution the use of early-developmental-stage cardiomyocytes to model adult-stage cells, particularly for dissecting metabolic perturbations emanating from LMNA mutations.
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影响因子：
64.8
作者：
Banks, Alexander S.;McAllister, Fiona E.;Camporez, Joao Paulo G.;Zushin, Peter-James H.;Jurczak, Michael J.;Laznik-Bogoslavski, Dina;Shulman, Gerald I.;Gygi, Steven P.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
5.5
作者：
Pan, Hubert;Richards, Ashleigh A.;Zhu, Xiaohui;Jogtar, Jose A.;Yin, Helen L.;Garg, Vidu
通讯作者：
Garg, Vidu
影响因子：
10.5
作者：
Rosen, ED;Hsu, CH;Spiegelman, BM
通讯作者：
Spiegelman, BM
DOI：
10.1073/pnas.072072599
发表时间：
2002-04-30
影响因子：
11.1
作者：
Li, L;Li, CY;Howe, GA
通讯作者：
Howe, GA
影响因子：
5.3
作者：
Rana, Ritu;Surapureddi, Sailesh;Goldstein, Joyce A.
通讯作者：
Goldstein, Joyce A.