Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.

Title

Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.

Creator

Li Tiangang; Chanda Dipanjan; Zhang Yanqiao; Choi Hueng-Sik; Chiang John Y L

Publisher

Journal of lipid research

Date

2010
2010-04

Description

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.

Subject

*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

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

832–842

Issue

4

Volume

51

Citation

Li Tiangang; Chanda Dipanjan; Zhang Yanqiao; Choi Hueng-Sik; Chiang John Y L, “Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.,” NEOMED Bibliography Database, accessed July 24, 2021, https://neomed.omeka.net/items/show/4874.

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