1
40
2
-
Text
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URL Address
<a href="http://doi.org/10.1016/j.jcmgh.2016.10.002" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.jcmgh.2016.10.002</a>
Pages
245–260
Issue
2
Volume
3
Dublin Core
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Title
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Targeting the Enterohepatic Bile Acid Signaling Induces Hepatic Autophagy via a
Publisher
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Cellular and molecular gastroenterology and hepatology
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-03
Subject
The topic of the resource
4EBP-1; ACAT; acyl-CoA:cholesterol acyltransferase; CE; chloroquine; Cholesterol; cholesterol 7alpha-hydroxylase; cholesterol ester; cholestyramine; Cholestyramine; ChTM; CQ; CYP7A1; diet-induced obesity; DIO; endoplasmic reticulum; ER; eukaryotic translation initiation factor 4E-binding protein 1; Fatty Liver; FC; free cholesterol; glycogen synthase kinase 3beta; GSK3beta; HMG-CoA reductase; HMGCR; LC3; LDLR; LMP; low-density lipoprotein receptor; lysosome membrane permeabilization; messenger RNA; microtubule-associated protein 1A/1B-light chain 3; mRNA; mTOR; Nuclear Receptor; phosphatidylinositol; PI; plasma membrane; PM; S6; SREBP; sterol response element binding protein; the nutrient sensing mechanistic target of rapamycin; tibosomal protein S6
Creator
An entity primarily responsible for making the resource
Wang Yifeng; Ding Yifeng; Li Jibiao; Chavan Hemantkumar; Matye David; Ni Hong-Min; Chiang John Y L; Krishnamurthy Partha; Ding Wen-Xing; Li Tiangang
Description
An account of the resource
BACKGROUND & AIMS: Hepatic cholesterol accumulation and autophagy defects contribute to hepatocyte injury in fatty liver disease. Bile acid synthesis is a major pathway for cholesterol catabolism in the liver. This study aims to understand the molecular link between cholesterol and bile acid metabolism and hepatic autophagy activity. METHODS: The effects of cholesterol and cholesterol 7alpha-hydroxylase (CYP7A1) expression on autophagy and lysosome function were studied in cell models. The effects and mechanism of disrupting enterohepatic bile acid circulation on hepatic autophagy were studied in mice. RESULTS: The results first showed differential regulation of hepatic autophagy by free cholesterol and cholesterol ester, whereby a modest increase of cellular free cholesterol, but not cholesterol ester, impaired lysosome function and caused marked autolysosome accumulation. We found that CYP7A1 induction, either by cholestyramine feeding in mice or adenovirus-mediated CYP7A1 expression in hepatocytes, caused strong autophagy induction. Mechanistically, we showed that CYP7A1 expression markedly attenuated growth factor/AKT signaling activation of mechanistic target of rapamycin (mTOR), but not amino acid signaling to mTOR in vitro and in vivo. Metabolomics analysis further found that CYP7A1 induction not only decreased hepatic cholesterol but also altered phospholipid and sphingolipid compositions. Collectively, these results suggest that CYP7A1 induction interferes with growth factor activation of AKT/mTOR signaling possibly by altering membrane lipid composition. Finally, we showed that cholestyramine feeding restored impaired hepatic autophagy and improved metabolic homeostasis in Western diet-fed mice. CONCLUSIONS: This study identified a novel CYP7A1-AKT-mTOR signaling axis that selectively induces hepatic autophagy, which helps improve hepatocellular integrity and metabolic homeostasis.
Identifier
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<a href="http://doi.org/10.1016/j.jcmgh.2016.10.002" target="_blank" rel="noreferrer noopener">10.1016/j.jcmgh.2016.10.002</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).
2017
4EBP-1
ACAT
acyl-CoA:cholesterol acyltransferase
CE
Cellular and molecular gastroenterology and hepatology
Chavan Hemantkumar
Chiang John Y L
chloroquine
Cholesterol
cholesterol 7alpha-hydroxylase
cholesterol ester
Cholestyramine
ChTM
CQ
CYP7A1
Department of Integrative Medical Sciences
diet-induced obesity
Ding Wen-Xing
Ding Yifeng
DIO
endoplasmic reticulum
ER
eukaryotic translation initiation factor 4E-binding protein 1
Fatty Liver
FC
free cholesterol
glycogen synthase kinase 3beta
GSK3beta
HMG-CoA reductase
HMGCR
Krishnamurthy Partha
LC3
LDLR
Li Jibiao
Li Tiangang
LMP
low-density lipoprotein receptor
lysosome membrane permeabilization
Matye David
messenger RNA
microtubule-associated protein 1A/1B-light chain 3
mRNA
mTOR
NEOMED College of Medicine
Ni Hong-Min
Nuclear Receptor
phosphatidylinositol
PI
plasma membrane
PM
S6
SREBP
sterol response element binding protein
the nutrient sensing mechanistic target of rapamycin
tibosomal protein S6
Wang Yifeng
-
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/10.1016/j.bbrc.2004.06.069" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bbrc.2004.06.069</a>
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
1204-1210
Issue
4
Volume
320
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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
Mechanisms of cholesterol and sterol regulatory element binding protein regulation of the sterol 12 alpha-hydroxylase gene (CYP8B1)
Publisher
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Biochemical and Biophysical Research Communications
Date
A point or period of time associated with an event in the lifecycle of the resource
2004
2004-08
Subject
The topic of the resource
bile acids; bile-acid metabolism; Biochemistry & Molecular Biology; Biophysics; cholesterol; CYP8B1; gene regulation; liver; mice; mouse; pathway; promoter; rat; receptor lxr-alpha; SREBP; srebps; suppresses
Creator
An entity primarily responsible for making the resource
Yang Y Z; Eggertsen G; Gafvels M; Andersson U; Einarsson C; Bjorkhem I; Chiang J Y L
Description
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Sterol 12alpha-hydroxylase (CYP8B1) is an obligatory enzyme for the synthesis of cholic acid and regulation of liver bile acid synthesis and intestine cholesterol absorption. The present study evaluates the roles for sterol regulatory element binding proteins (SREBPs) in the regulation of the CYP8B1 gene. Cholesterol feeding of mice and rats decreased the activity of CYP8B1, contrary to the up-regulation of cholesterol 7alpha-hydroxylase (CYP7A1). Cholesterol feeding also reduced mRNA levels for SREBP-1 but not for SREBP-2 in rat livers. Cholesterol and 25-hydroxycholesterol decreased the CYP8B1/luciferase reporter activity. Co-transfection of SREBP-1a and -1c stimulated CYP8B1 promoter activity, while SREBP-2 did not have any effects. Electrophoretic mobility shift assay and mutagenesis analyses identified several functional sterol regulatory elements (SRE) and E-box motifs in the rat CYP8B1 promoter. Our results indicate that SREBP-1a and -1c enhance transcription of the CYP8B1 gene through binding to SRE. Cholesterol loading reduces SREBP-1 mRNA expression in addition to reducing functional SREBP-1 protein, and results in decreasing CYP8B1 gene transcription. (C) 2004 Elsevier Inc. All rights reserved.
Identifier
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<a href="http://doi.org/10.1016/j.bbrc.2004.06.069" target="_blank" rel="noreferrer noopener">10.1016/j.bbrc.2004.06.069</a>
Format
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Journal Article
2004
Andersson U
BILE acids
bile-acid metabolism
Biochemical and biophysical research communications
Biochemistry & Molecular Biology
Biophysics
Bjorkhem I
Chiang J Y L
Cholesterol
CYP8B1
Eggertsen G
Einarsson C
Gafvels M
Gene Regulation
Journal Article
Liver
Mice
mouse
pathway
promoter
rat
receptor lxr-alpha
SREBP
srebps
suppresses
Yang Y Z