Hepatic FoxO1 Acetylation Is Involved in Oleanolic Acid-Induced Memory of Glycemic Control: Novel Findings from Study 2
文献类型：期刊论文
| 作者 | Zhou, Xiu1,2; Zeng, Xiao-Yi1,2; Wang, Hao1,2; Li, Songpei1,2; Jo, Eunjung1,2; Xue, Charlie C. L.1,2; Tan, Minjia3 ; Molero, Juan C.1,2; Ye, Ji-Ming1,2
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| 刊名 | PLOS ONE
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| 出版日期 | 2014-09-15 |
| 卷号 | 9期号:9 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0107231 |
| 文献子类 | Article |
| 英文摘要 | Our recent study (referred as Study 1) showed that the triterpenoid oleanolic acid (OA) was able to produce a sustained correction of hyperglycemia beyond treatment period in type 2 diabetes (T2D) mice with liver as a responsible site. To follow up the previous observations, the present study (referred as Study 2) investigated the possible role of acetylation of FoxO1 and associated events in this therapeutic memory by characterizing the pathways regulating the acetylation status during and post-OA treatments. OA treatment (100 mg/kg/day for 4 weeks, during OA treatment) reduced hyperglycemia in T2D mice by similar to 87% and this effect was largely (similar to 70%) maintained even 4 weeks after the cessation of OA administration (post-OA treatment). During OA treatment, the acetylation and phosphorylation of FoxO1 were markedly increased (1.5 to 2.5-fold) while G6Pase expression was suppressed by similar to 80%. Consistent with this, OA treatment reversed pyruvate intolerance in high-fat fed mice. Histone acetyltransferase 1 (HAT1) content was increased (>50%) and histone deacetylases (HDACs) 4 and 5 (not HDAC1) were reduced by 30-50%. The OA-induced changes in FoxO1, G6Pase, HAT1 and HDACs persisted during the post-OA treatment period when the increased phosphorylation of AMPK, SIRT1 content and reduced liver triglyceride had subsided. These results confirmed the ability of OA to control hyperglycemia far beyond treatment period in T2D mice. Most importantly, in the present study we demonstrated acetylation of FoxO1 in the liver is involved in OA-induced memory for the control of hyperglycemia. Our novel findings suggest that acetylation of the key regulatory proteins of hepatic gluconeogenesis is a plausible mechanism by the triterpenoid to achieve a sustained glycemic control for T2D. |
| WOS关键词 | ACTIVATED PROTEIN-KINASE ; TRANSCRIPTION FACTOR FOXO1 ; HISTONE DEACETYLASE 4 ; INSULIN SENSITIVITY ; SKELETAL-MUSCLE ; DNA-BINDING ; AMP ; PHOSPHORYLATION ; LOCALIZATION ; GLUCOSE |
| 资助项目 | National Health and Medical Research Council of Australia Program[535921] ; Australian Research Council Funding[DP110102396] ; RMIT VC fellowship[00000000] ; Australian Postgraduate Scholarship[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000341774800052 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276903]  |
| 专题 | 化学蛋白质组学研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ye, Ji-Ming |
| 作者单位 | 1.RMIT Univ, Hlth Innovat Res Inst, Melbourne, Vic, Australia; 2.RMIT Univ, Sch Hlth Sci, Melbourne, Vic, Australia; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Xiu,Zeng, Xiao-Yi,Wang, Hao,et al. Hepatic FoxO1 Acetylation Is Involved in Oleanolic Acid-Induced Memory of Glycemic Control: Novel Findings from Study 2[J]. PLOS ONE,2014,9(9). |
| APA | Zhou, Xiu.,Zeng, Xiao-Yi.,Wang, Hao.,Li, Songpei.,Jo, Eunjung.,...&Ye, Ji-Ming.(2014).Hepatic FoxO1 Acetylation Is Involved in Oleanolic Acid-Induced Memory of Glycemic Control: Novel Findings from Study 2.PLOS ONE,9(9). |
| MLA | Zhou, Xiu,et al."Hepatic FoxO1 Acetylation Is Involved in Oleanolic Acid-Induced Memory of Glycemic Control: Novel Findings from Study 2".PLOS ONE 9.9(2014). |
入库方式： OAI收割
来源：上海药物研究所
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