共查询到20条相似文献,搜索用时 15 毫秒
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Park JM Kim TH Bae JS Kim MY Kim KS Ahn YH 《Biochemical and biophysical research communications》2010,403(3-4):329-334
During a state of fasting, the blood glucose level is maintained by hepatic gluconeogenesis. SIRT1 is an important metabolic regulator during nutrient deprivation and the liver-specific knockdown of SIRT1 resulted in decreased glucose production. We hypothesize that SIRT1 is responsible for the upregulation of insulin-suppressed gluconeogenic genes through the deacetylation of FOXO1. Treatment of primary cultured hepatocytes with resveratrol increased insulin-repressed PEPCK and G6Pase mRNA levels, which depend on SIRT1 activity. We found that the resveratrol treatment resulted in a decrease in the phosphorylation of Akt and FOXO1, which are independent of SIRT1 action. Fluorescence microscopy revealed that resveratrol caused the nuclear localization of FOXO1. In the nucleus, FOXO1 is deacetylated by SIRT1, which might make it more accessible to the IRE of the PEPCK and G6Pase promoter, causing an increase in their gene expression. Our results indicate that resveratrol upregulates the expression of gluconeogenic genes by attenuating insulin signaling and by deacetylating FOXO1, which are SIRT1-independent in the cytosol and SIRT1-dependent in the nucleus, respectively. 相似文献
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Burgess SC Leone TC Wende AR Croce MA Chen Z Sherry AD Malloy CR Finck BN 《The Journal of biological chemistry》2006,281(28):19000-19008
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PGC-1beta in the regulation of hepatic glucose and energy metabolism 总被引:14,自引:0,他引:14
Lin J Tarr PT Yang R Rhee J Puigserver P Newgard CB Spiegelman BM 《The Journal of biological chemistry》2003,278(33):30843-30848
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Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice 总被引:26,自引:0,他引:26
Lin J Wu PH Tarr PT Lindenberg KS St-Pierre J Zhang CY Mootha VK Jäger S Vianna CR Reznick RM Cui L Manieri M Donovan MX Wu Z Cooper MP Fan MC Rohas LM Zavacki AM Cinti S Shulman GI Lowell BB Krainc D Spiegelman BM 《Cell》2004,119(1):121-135
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Yin H Hu M Zhang R Shen Z Flatow L You M 《The Journal of biological chemistry》2012,287(13):9817-9826
Ethanol-mediated inhibition of hepatic sirtuin 1 (SIRT1) plays a crucial role in the pathogenesis of alcoholic fatty liver disease. Here, we investigated the underlying mechanisms of this inhibition by identifying a new hepatic target of ethanol action, microRNA-217 (miR-217). The role of miR-217 in the regulation of the effects of ethanol was investigated in cultured mouse AML-12 hepatocytes and in the livers of chronically ethanol-fed mice. In AML-12 hepatocytes and in mouse livers, chronic ethanol exposure drastically and specifically induced miR-217 levels and caused excess fat accumulation. Further studies revealed that overexpression of miR-217 in AML-12 cells promoted ethanol-mediated impairments of SIRT1 and SIRT1-regulated genes encoding lipogenic or fatty acid oxidation enzymes. More importantly, miR-217 impairs functions of lipin-1, a vital lipid regulator, in hepatocytes. Taken together, our novel findings suggest that miR-217 is a specific target of ethanol action in the liver and may present as a potential therapeutic target for treating human alcoholic fatty liver disease. 相似文献