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Role of resveratrol in FOXO1-mediated gluconeogenic gene expression in the liver.

Authors
 Joo-Man Park  ;  Tae-Hyun Kim  ;  Jin-Sik Bae  ;  Mi-Young Kim  ;  Kyung-Sup Kim  ;  Yong-Ho Ahn 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.403(3-4) : 329-334, 2010 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2010
MeSH
Animals ; Antioxidants/pharmacology* ; Forkhead Box Protein O1 ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism* ; Gene Expression/drug effects* ; Gluconeogenesis/drug effects* ; Gluconeogenesis/genetics ; Humans ; Liver/drug effects* ; Liver/metabolism ; Phosphorylation ; RNA, Small Interfering/genetics ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/genetics ; Sirtuin 1/metabolism ; Stilbenes/pharmacology* ; Up-Regulation
Keywords
Resveratrol ; FOXO1 ; SIRT1 ; Gluconeogenesis
Abstract
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X10020760
DOI
10.1016/j.bbrc.2010.11.028
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Mi Young(김미영)
Kim, Tae Hyun(김태현)
Park, Joo Man(박주만)
Bae, Jin Sik(배진식)
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103188
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