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Text
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URL Address
<a href="http://doi.org/10.1194/jlr.M002782" target="_blank" rel="noreferrer noopener">http://doi.org/10.1194/jlr.M002782</a>
Pages
832–842
Issue
4
Volume
51
Dublin Core
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Title
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Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.
Publisher
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Journal of lipid research
Date
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2010
2010-04
Subject
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*Gene Expression Regulation; Acetylation; AMP-Activated Protein Kinases/metabolism; ATP Citrate (pro-S)-Lyase/genetics/metabolism; Bile Acids and Salts/metabolism; Cells; Cholesterol 7-alpha-Hydroxylase/genetics/*metabolism; Cultured; DNA-Binding Proteins/metabolism; Enzymologic; Epigenesis; Genes; Genetic; Glucose/*administration & dosage; Hep G2 Cells; Hepatocyte Nuclear Factor 4/metabolism; Hepatocytes/*enzymology/metabolism; Histones/metabolism; Humans; Hyperglycemia/enzymology/*metabolism; Messenger/metabolism; Methylation; Reporter; RNA; RNA Interference
Creator
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Li Tiangang; Chanda Dipanjan; Zhang Yanqiao; Choi Hueng-Sik; Chiang John Y L
Description
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Bile acids play important roles in the regulation of lipid, glucose, and energy homeostasis. Recent studies suggest that glucose regulates gene transcription in the liver. The aim of this study was to investigate the potential role of glucose in regulation of bile acid synthesis in human hepatocytes. High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory gene in bile acid synthesis. Activation of an AMP-activated protein kinase (AMPK) decreased CYP7A1 mRNA, hepatocyte nuclear factor 4alpha (HNF4alpha) protein, and binding to CYP7A1 chromatin. Glucose increased ATP levels to inhibit AMPK and induce HNF4alpha to stimulate CYP7A1 gene transcription. Furthermore, glucose increased histone acetylation and decreased H3K9 di- and tri-methylation in the CYP7A1 chromatin. Knockdown of ATP-citrate lyase, which converts citrate to acetyl-CoA, decreased histone acetylation and attenuated glucose induction of CYP7A1 mRNA expression. These results suggest that glucose signaling also induces CYP7A1 gene transcription by epigenetic regulation of the histone acetylation status. This study uncovers a novel link between hepatic glucose metabolism and bile acid synthesis. Glucose induction of bile acid synthesis may have an important implication in metabolic control of glucose, lipid, and energy homeostasis under normal and diabetic conditions.
Identifier
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<a href="http://doi.org/10.1194/jlr.M002782" target="_blank" rel="noreferrer noopener">10.1194/jlr.M002782</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Gene Expression Regulation
2010
Acetylation
AMP-Activated Protein Kinases/metabolism
ATP Citrate (pro-S)-Lyase/genetics/metabolism
Bile Acids and Salts/metabolism
Cells
Chanda Dipanjan
Chiang John Y L
Choi Hueng-Sik
Cholesterol 7-alpha-Hydroxylase/genetics/*metabolism
Cultured
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
Enzymologic
Epigenesis
Genes
Genetic
Glucose/*administration & dosage
Hep G2 Cells
Hepatocyte Nuclear Factor 4/metabolism
Hepatocytes/*enzymology/metabolism
Histones/metabolism
Humans
Hyperglycemia/enzymology/*metabolism
Journal of lipid research
Li Tiangang
Messenger/metabolism
Methylation
NEOMED College of Medicine
Reporter
RNA
RNA Interference
Zhang Yanqiao