Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2.
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 (refer...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4164604?pdf=render |
| _version_ | 1811326724164550656 |
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| author | Xiu Zhou Xiao-Yi Zeng Hao Wang Songpei Li Eunjung Jo Charlie C L Xue Minjia Tan Juan C Molero Ji-Ming Ye |
| author_facet | Xiu Zhou Xiao-Yi Zeng Hao Wang Songpei Li Eunjung Jo Charlie C L Xue Minjia Tan Juan C Molero Ji-Ming Ye |
| author_sort | Xiu Zhou |
| collection | DOAJ |
| description | 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 ∼87% and this effect was largely (∼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 ∼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. |
| first_indexed | 2024-04-13T14:53:47Z |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T14:53:47Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-c413cc33a0854795a8d4302e82d4feb02022-12-22T02:42:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10723110.1371/journal.pone.0107231Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2.Xiu ZhouXiao-Yi ZengHao WangSongpei LiEunjung JoCharlie C L XueMinjia TanJuan C MoleroJi-Ming YeOur 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 ∼87% and this effect was largely (∼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 ∼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.http://europepmc.org/articles/PMC4164604?pdf=render |
| spellingShingle | Xiu Zhou Xiao-Yi Zeng Hao Wang Songpei Li Eunjung Jo Charlie C L Xue Minjia Tan Juan C Molero Ji-Ming Ye Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2. PLoS ONE |
| title | Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2. |
| title_full | Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2. |
| title_fullStr | Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2. |
| title_full_unstemmed | Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2. |
| title_short | Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from Study 2. |
| title_sort | hepatic foxo1 acetylation is involved in oleanolic acid induced memory of glycemic control novel findings from study 2 |
| url | http://europepmc.org/articles/PMC4164604?pdf=render |
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