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Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from study 2

Zhou, Xiu, Zeng, Xiao-Yi, Wang, Hao, Li, Songpei, Jo, Eunjung, Xue, Charlie C. L., Tan, Minjia, Molero Navajas, Juan C. and Ye, Ji-Ming 2014, Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from study 2, PLoS one, vol. 9, no. 9, pp. 1-11, doi: 10.1371/journal.pone.0107231.

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Title Hepatic FoxO1 acetylation is involved in oleanolic acid-induced memory of glycemic control: novel findings from study 2
Author(s) Zhou, Xiu
Zeng, Xiao-Yi
Wang, Hao
Li, Songpei
Jo, Eunjung
Xue, Charlie C. L.
Tan, Minjia
Molero Navajas, Juan C.
Ye, Ji-Ming
Journal name PLoS one
Volume number 9
Issue number 9
Article ID e107231
Start page 1
End page 11
Total pages 11
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2014-09-15
ISSN 1932-6203
Keyword(s) Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
ACTIVATED PROTEIN-KINASE
TRANSCRIPTION FACTOR FOXO1
HISTONE DEACETYLASE 4
INSULIN SENSITIVITY
SKELETAL-MUSCLE
DNA-BINDING
AMP
PHOSPHORYLATION
LOCALIZATION
GLUCOSE
Summary 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.
Language eng
DOI 10.1371/journal.pone.0107231
Field of Research MD Multidisciplinary
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2014, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30112106

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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