共查询到20条相似文献,搜索用时 15 毫秒
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Miyazaki M Dobrzyn A Man WC Chu K Sampath H Kim HJ Ntambi JM 《The Journal of biological chemistry》2004,279(24):25164-25171
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Sterol regulatory element-binding protein-1 is regulated by glucose at the transcriptional level 总被引:10,自引:0,他引:10
Hasty AH Shimano H Yahagi N Amemiya-Kudo M Perrey S Yoshikawa T Osuga J Okazaki H Tamura Y Iizuka Y Shionoiri F Ohashi K Harada K Gotoda T Nagai R Ishibashi S Yamada N 《The Journal of biological chemistry》2000,275(40):31069-31077
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Protein-tyrosine phosphatase 1B as new activator for hepatic lipogenesis via sterol regulatory element-binding protein-1 gene expression 总被引:7,自引:0,他引:7
Shimizu S Ugi S Maegawa H Egawa K Nishio Y Yoshizaki T Shi K Nagai Y Morino K Nemoto K Nakamura T Bryer-Ash M Kashiwagi A 《The Journal of biological chemistry》2003,278(44):43095-43101
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p38 mitogen-activated protein kinase plays an inhibitory role in hepatic lipogenesis 总被引:1,自引:0,他引:1
Xiong Y Collins QF An J Lupo E Liu HY Liu D Robidoux J Liu Z Cao W 《The Journal of biological chemistry》2007,282(7):4975-4982
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SIRT1 Deacetylates and Inhibits SREBP-1C Activity in Regulation of Hepatic Lipid Metabolism 总被引:1,自引:0,他引:1
Bhaskar Ponugoti Dong-Hyun Kim Zhen Xiao Zachary Smith Ji Miao Mengwei Zang Shwu-Yuan Wu Cheng-Ming Chiang Timothy D. Veenstra Jongsook Kim Kemper 《The Journal of biological chemistry》2010,285(44):33959-33970
The SIRT1 deacetylase inhibits fat synthesis and stimulates fat oxidation in response to fasting, but the underlying mechanisms remain unclear. Here we report that SREBP-1c, a key lipogenic activator, is an in vivo target of SIRT1. SIRT1 interaction with SREBP-1c was increased during fasting and decreased upon feeding, and consistently, SREBP-1c acetylation levels were decreased during fasting in mouse liver. Acetylated SREBP-1c levels were also increased in HepG2 cells treated with insulin and glucose to mimic feeding conditions, and down-regulation of p300 by siRNA decreased the acetylation. Depletion of hepatic SIRT1 by adenoviral siRNA increased acetylation of SREBP-1c with increased lipogenic gene expression. Tandem mass spectrometry and mutagenesis studies revealed that SREBP-1c is acetylated by p300 at Lys-289 and Lys-309. Mechanistic studies using acetylation-defective mutants showed that SIRT1 deacetylates and inhibits SREBP-1c transactivation by decreasing its stability and its occupancy at the lipogenic genes. Remarkably, SREBP-1c acetylation levels were elevated in diet-induced obese mice, and hepatic overexpression of SIRT1 or treatment with resveratrol, a SIRT1 activator, daily for 1 week decreased acetylated SREBP-1c levels with beneficial functional outcomes. These results demonstrate an intriguing connection between elevated SREBP-1c acetylation and increased lipogenic gene expression, suggesting that abnormally elevated SREBP-1c acetylation increases SREBP-1c lipogenic activity in obese mice. Reducing acetylation of SREBP-1c by targeting SIRT1 may be useful for treating metabolic disorders, including fatty liver, obesity, and type II diabetes. 相似文献
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