1
40
4
-
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
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.
Publisher
An entity responsible for making the resource available
Journal of lipid research
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-04
Subject
The topic of the resource
*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
An entity primarily responsible for making the resource
Li Tiangang; Chanda Dipanjan; Zhang Yanqiao; Choi Hueng-Sik; Chiang John Y L
Description
An account of the resource
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
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1194/jlr.M002782" target="_blank" rel="noreferrer noopener">10.1194/jlr.M002782</a>
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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
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1136/gutjnl-2012-303347" target="_blank" rel="noreferrer noopener">http://doi.org/10.1136/gutjnl-2012-303347</a>
Pages
1044–1054
Issue
7
Volume
62
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Estrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol.
Publisher
An entity responsible for making the resource available
Gut
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
2013-07
Subject
The topic of the resource
Alcohol-Induced Injury; Alcoholic Liver Disease; Alcoholic/genetics/*metabolism/prevention & control; Animals; Cannabinoid; CB1/*physiology; Cytochrome P-450 CYP2E1 Inhibitors; Cytochrome P-450 CYP2E1/genetics/*metabolism; Enzyme Inhibitors/pharmacology/therapeutic use; Enzymologic/drug effects/physiology; Estrogen/deficiency/genetics/*physiology; Ethanol/pharmacology; Gene Expression Profiling/methods; Gene Expression Regulation; Gene Regulation; Genetic/physiology; Inbred C57BL; Knockout; Liver; Liver Diseases; Liver Metabolism; Liver/metabolism; Male; Mice; Oxidation-Reduction; Oxidative Stress/physiology; Receptor; Receptors; Signal Transduction/drug effects/physiology; Tamoxifen/analogs & derivatives/pharmacology/therapeutic use; Transcription
Creator
An entity primarily responsible for making the resource
Kim Don-Kyu; Kim Yong-Hoon; Jang Hyun-Hee; Park Jinyoung; Kim Jung Ran; Koh Minseob; Jeong Won-Il; Koo Seung-Hoi; Park Tae-Sik; Yun Chul-Ho; Park Seung Bum; Chiang John Y L; Lee Chul-Ho; Choi Hueng-Sik
Description
An account of the resource
BACKGROUND: The hepatic endocannabinoid system and cytochrome P450 2E1 (CYP2E1), a key enzyme causing alcohol-induced reactive oxygen species (ROS) generation, are major contributors to the pathogenesis of alcoholic liver disease. The nuclear hormone receptor oestrogen-related receptor gamma (ERRgamma) is a constitutively active transcriptional activator regulating gene expression. OBJECTIVE: To investigate the role of ERRgamma in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRgamma inverse agonist. DESIGN: For chronic alcoholic hepatosteatosis study, C57BL/6J wild-type and CB1(-/-) mice were administered alcohol for 4 weeks. GSK5182 and chlormethiazole (CMZ) were given by oral gavage for the last 2 weeks of alcohol feeding. Gene expression profiles and biochemical assays were performed using the liver or blood of mice. RESULTS: Hepatic ERRgamma gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRgamma gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRgamma inverse agonist significantly ameliorates chronic alcohol-induced liver injury in mice through inhibition of CYP2E1-mediated generation of ROS, while inhibition of CYP2E1 by CMZ abrogates the beneficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERRgamma and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1(-/-) mice. CONCLUSIONS: ERRgamma, as a previously unrecognised transcriptional regulator of hepatic CB1 receptor, controls alcohol-induced oxidative stress and liver injury through CYP2E1 induction, and its inverse agonist could ameliorate oxidative liver injury due to chronic alcohol exposure.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1136/gutjnl-2012-303347" target="_blank" rel="noreferrer noopener">10.1136/gutjnl-2012-303347</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2013
Alcohol-Induced Injury
Alcoholic Liver Disease
Alcoholic/genetics/*metabolism/prevention & control
Animals
Cannabinoid
CB1/*physiology
Chiang John Y L
Choi Hueng-Sik
Cytochrome P-450 CYP2E1 Inhibitors
Cytochrome P-450 CYP2E1/genetics/*metabolism
Department of Integrative Medical Sciences
Enzyme Inhibitors/pharmacology/therapeutic use
Enzymologic/drug effects/physiology
Estrogen/deficiency/genetics/*physiology
Ethanol/pharmacology
Gene Expression Profiling/methods
Gene Expression Regulation
Gene Regulation
Genetic/physiology
Gut
Inbred C57BL
Jang Hyun-Hee
Jeong Won-Il
Kim Don-Kyu
Kim Jung Ran
Kim Yong-Hoon
Knockout
Koh Minseob
Koo Seung-Hoi
Lee Chul-Ho
Liver
Liver Diseases
Liver Metabolism
Liver/metabolism
Male
Mice
NEOMED College of Medicine
Oxidation-Reduction
Oxidative Stress/physiology
Park Jinyoung
Park Seung Bum
Park Tae-Sik
Receptor
Receptors
Signal Transduction/drug effects/physiology
Tamoxifen/analogs & derivatives/pharmacology/therapeutic use
Transcription
Yun Chul-Ho
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1042/BJ20141494" target="_blank" rel="noreferrer noopener">http://doi.org/10.1042/BJ20141494</a>
Pages
181–193
Issue
2
Volume
470
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Orphan nuclear receptor oestrogen-related receptor gamma (ERRgamma) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression.
Publisher
An entity responsible for making the resource available
The Biochemical journal
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015-09
Subject
The topic of the resource
Animals; bile acid; Bile Acids and Salts/metabolism; Cannabinoid; cannabinoid receptors; CB1/agonists/genetics/*metabolism; Cells; Cholesterol 7-alpha-Hydroxylase/*biosynthesis/genetics; cholesterol 7alpha-hydroxylase (CYP7A1); Cultured; Cytoplasmic and Nuclear/metabolism; Drug Inverse Agonism; Estrogen/genetics/*metabolism; Ethanol/pharmacology; Gene Expression; Genetic; Glycerides/pharmacology; GSK5182; HEK293 Cells; Hepatocytes/metabolism; Humans; Inbred C57BL; Knockout; Liver/*metabolism; Mice; oestrogen-related receptor gamma (ERRgamma); orphan nuclear receptor; Promoter Regions; Rats; Receptor; Receptors; small heterodimer partner (SHP); Sprague-Dawley; Transcription
Creator
An entity primarily responsible for making the resource
Zhang Yaochen; Kim Don-Kyu; Lee Ji-Min; Park Seung Bum; Jeong Won-Il; Kim Seong Heon; Lee In-Kyu; Lee Chul-Ho; Chiang John Y L; Choi Hueng-Sik
Description
An account of the resource
Bile acids are primarily synthesized from cholesterol in the liver and have important roles in dietary lipid absorption and cholesterol homoeostasis. Detailed roles of the orphan nuclear receptors regulating cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis, have not yet been fully elucidated. In the present study, we report that oestrogen-related receptor gamma (ERRgamma) is a novel transcriptional regulator of CYP7A1 expression. Activation of cannabinoid receptor type 1 (CB1 receptor) signalling induced ERRgamma-mediated transcription of the CYP7A1 gene. Overexpression of ERRgamma increased CYP7A1 expression in vitro and in vivo, whereas knockdown of ERRgamma attenuated CYP7A1 expression. Deletion analysis of the CYP7A1 gene promoter and a ChIP assay revealed an ERRgamma-binding site on the CYP7A1 gene promoter. Small heterodimer partner (SHP) inhibited the transcriptional activity of ERRgamma and thus regulated CYP7A1 expression. Overexpression of ERRgamma led to increased bile acid levels, whereas an inverse agonist of ERRgamma, GSK5182, reduced CYP7A1 expression and bile acid synthesis. Finally, GSK5182 significantly reduced hepatic CB1 receptor-mediated induction of CYP7A1 expression and bile acid synthesis in alcohol-treated mice. These results provide the molecular mechanism linking ERRgamma and bile acid metabolism.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1042/BJ20141494" target="_blank" rel="noreferrer noopener">10.1042/BJ20141494</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2015
Animals
bile acid
Bile Acids and Salts/metabolism
Cannabinoid
cannabinoid receptors
CB1/agonists/genetics/*metabolism
Cells
Chiang John Y L
Choi Hueng-Sik
Cholesterol 7-alpha-Hydroxylase/*biosynthesis/genetics
cholesterol 7alpha-hydroxylase (CYP7A1)
Cultured
Cytoplasmic and Nuclear/metabolism
Department of Integrative Medical Sciences
Drug Inverse Agonism
Estrogen/genetics/*metabolism
Ethanol/pharmacology
Gene Expression
Genetic
Glycerides/pharmacology
GSK5182
HEK293 Cells
Hepatocytes/metabolism
Humans
Inbred C57BL
Jeong Won-Il
Kim Don-Kyu
Kim Seong Heon
Knockout
Lee Chul-Ho
Lee In-Kyu
Lee Ji-Min
Liver/*metabolism
Mice
NEOMED College of Medicine
oestrogen-related receptor gamma (ERRgamma)
orphan nuclear receptor
Park Seung Bum
Promoter Regions
Rats
Receptor
Receptors
small heterodimer partner (SHP)
Sprague-Dawley
The Biochemical journal
Transcription
Zhang Yaochen
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/hep4.1129" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep4.1129</a>
Pages
99–112
Issue
1
Volume
2
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Deficiency of cholesterol 7alpha-hydroxylase in bile acid synthesis exacerbates alcohol-induced liver injury in mice.
Publisher
An entity responsible for making the resource available
Hepatology communications
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-01
Creator
An entity primarily responsible for making the resource
Donepudi Ajay C; Ferrell Jessica M; Boehme Shannon; Choi Hueng-Sik; Chiang John Y L
Description
An account of the resource
Alcoholic fatty liver disease (AFLD) is a major risk factor for cirrhosis-associated liver diseases. Studies demonstrate that alcohol increases serum bile acids in humans and rodents. AFLD has been linked to cholestasis, although the physiologic relevance of increased bile acids in AFLD and the underlying mechanism of increasing the bile acid pool by alcohol feeding are still unclear. In this study, we used mouse models either deficient of or overexpressing cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting and key regulatory enzyme in bile acid synthesis, to study the effect of alcohol drinking in liver metabolism and inflammation. Mice were challenged with chronic ethanol feeding (10 days) plus a binge dose of alcohol by oral gavage (5 g/kg body weight). Alcohol feeding reduced bile acid synthesis gene expression but increased the bile acid pool size, hepatic triglycerides and cholesterol, and inflammation and injury in wild-type mice and aggravated liver inflammation and injury in Cyp7a1-deficient mice. Interestingly, alcohol-induced hepatic inflammation and injury were ameliorated in Cyp7a1 transgenic mice. Conclusion: Alcohol feeding alters hepatic bile acid and cholesterol metabolism to cause liver inflammation and injury, while maintenance of bile acid and cholesterol homeostasis protect against alcohol-induced hepatic inflammation and injury. Our findings indicate that CYP7A1 plays a key role in protection against alcohol-induced steatohepatitis. (Hepatology Communications 2018;2:99-112).
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep4.1129" target="_blank" rel="noreferrer noopener">10.1002/hep4.1129</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).
2018
Boehme Shannon
Chiang John Y L
Choi Hueng-Sik
Department of Integrative Medical Sciences
Donepudi Ajay C
Ferrell Jessica M
Hepatology communications
NEOMED College of Medicine