Selective inhibition of CBP/p300 HAT by A-485 results in suppression of lipogenesis and hepatic gluconeogenesis
Selective inhibition of CBP/p300 HAT by A-485 results in suppression of lipogenesis and hepatic gluconeogenesis
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A-485 对 CBP/p300 HAT 的选择性抑制导致脂肪生成和肝糖异生的抑制
DOI：
10.1038/s41419-020-02960-6
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发表时间：
2020-09
影响因子：
9
通讯作者：
Xiao Wang
中科院分区：
文献类型：
--
作者：
Kecheng Zhu;Linlin Zhang;Ruyuan Deng;Libin Zhou;Qianqian Liu;Guoyue Yuan;Feiye Zhou;Shushu Wang;Yun Liu;Qin Zhu;Xiao Wang
组蛋白乙酰转移酶CREB结合蛋白（CBP）及其旁系同型P300是转录共激活剂，对于多种信号通路和能量稳态至关重要。但是，CBP/P300 HAT域在调节能量中的作用
The histone acetyltransferases CREB-binding protein (CBP) and its paralogue p300 are transcriptional coactivators which are essential for a multitude of signaling pathways and energy homeostasis. However, the role of CBP/p300 HAT domain in regulating energy balance is still unclear. Here, C57BL/6 mice fed with either normal chow diet (NCD) or high-fat diet (HFD) were administrated with A-485, a recently reported selective inhibitor of CBP/p300 HAT activity for 1 week and the metabolic change was analyzed. The white adipose tissue (WAT) weight and adipocyte size were reduced in A-485-administrated mice, with decreased expressions of lipogenic genes and transcriptional factors. In the liver of A-485-treated mice, the lipid content and lipogenic gene expressions were lowered while the binding of forkhead box O1 (FOXO1) to glucose-6-phosphatase (G6Pc) promoter was reduced, leading to decreased expression of G6Pc. In primary mouse hepatocytes, A-485 abolished cAMP-elicited mRNA expressions of key gluconeogenic enzymes and promoted FOXO1 protein degradation via increasing its ubiquitination. Thus, A-485 inhibits lipogenesis in WAT and liver as well as decreases hepatic glucose production via preventing FOXO1 acetylation, leading to its protein degradation through a proteasome-dependent pathway. The specific inhibition of CBP/p300 HAT will provide a novel therapeutic approach for metabolic diseases.
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影响因子：
11.4
作者：
Xu, Wu;Kasper, Lawryn H.;Brindle, Paul K.
通讯作者：
Brindle, Paul K.
影响因子：
64.8
作者：
Lasko LM;Jakob CG;Edalji RP;Qiu W;Montgomery D;Digiammarino EL;Hansen TM;Risi RM;Frey R;Manaves V;Shaw B;Algire M;Hessler P;Lam LT;Uziel T;Faivre E;Ferguson D;Buchanan FG;Martin RL;Torrent M;Chiang GG;Karukurichi K;Langston JW;Weinert BT;Choudhary C;de Vries P;Van Drie JH;McElligott D;Kesicki E;Marmorstein R;Sun C;Cole PA;Rosenberg SH;Michaelides MR;Lai A;Bromberg KD
通讯作者：
Bromberg KD
影响因子：
4.8
作者：
Qiang, Li;Banks, Alexander S.;Accili, Domenico
通讯作者：
Accili, Domenico
影响因子：
16
作者：
Z. Wu;E. Rosen;R. Brun;S. Hauser;G. Adelmant;A. Troy;C. McKeon;G. Darlington;B. Spiegelman
通讯作者：
Z. Wu;E. Rosen;R. Brun;S. Hauser;G. Adelmant;A. Troy;C. McKeon;G. Darlington;B. Spiegelman
DOI：
10.1152/ajpendo.00249.2012
发表时间：
2012-11-01
影响因子：
5.1
作者：
Ip, Wilfred;Shao, Weijuan;Jin, Tianru
通讯作者：
Jin, Tianru