Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S]
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...
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doaj-7b96740c97de441f8a5a4f22d4632d6c2021-04-28T05:55:25ZengElsevierJournal of Lipid Research0022-22752010-04-01514832842Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S]Tiangang Li0Dipanjan Chanda1Yanqiao Zhang2Hueng-Sik Choi3John Y.L. Chiang4Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH, 44272Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of KoreaDepartment of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH, 44272Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of KoreaTo whom correspondence should be addressed; Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH, 44272Bile 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 7α-hydroxylase (CYP7A1), the key regulatory gene in bile acid synthesis. Activation of an AMP-activated protein kinase (AMPK) decreased CYP7A1 mRNA, hepatocyte nuclear factor 4α (HNF4α) protein, and binding to CYP7A1 chromatin. Glucose increased ATP levels to inhibit AMPK and induce HNF4α 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.http://www.sciencedirect.com/science/article/pii/S0022227520304934CYP7A1bile acid synthesisAMPKnuclear receptorsglucoseepigenetic |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tiangang Li Dipanjan Chanda Yanqiao Zhang Hueng-Sik Choi John Y.L. Chiang |
spellingShingle |
Tiangang Li Dipanjan Chanda Yanqiao Zhang Hueng-Sik Choi John Y.L. Chiang Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S] Journal of Lipid Research CYP7A1 bile acid synthesis AMPK nuclear receptors glucose epigenetic |
author_facet |
Tiangang Li Dipanjan Chanda Yanqiao Zhang Hueng-Sik Choi John Y.L. Chiang |
author_sort |
Tiangang Li |
title |
Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S] |
title_short |
Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S] |
title_full |
Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S] |
title_fullStr |
Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S] |
title_full_unstemmed |
Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[S] |
title_sort |
glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2010-04-01 |
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 7α-hydroxylase (CYP7A1), the key regulatory gene in bile acid synthesis. Activation of an AMP-activated protein kinase (AMPK) decreased CYP7A1 mRNA, hepatocyte nuclear factor 4α (HNF4α) protein, and binding to CYP7A1 chromatin. Glucose increased ATP levels to inhibit AMPK and induce HNF4α 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. |
topic |
CYP7A1 bile acid synthesis AMPK nuclear receptors glucose epigenetic |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520304934 |
work_keys_str_mv |
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