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Text
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URL Address
<a href="http://doi.org/10.1002/hep.26699" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.26699</a>
Pages
1750–1760
Issue
5
Volume
59
Dublin Core
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Title
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All-trans-retinoic acid ameliorates hepatic steatosis in mice by a novel transcriptional cascade.
Publisher
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Hepatology (Baltimore, Md.)
Date
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2014
2014-05
Subject
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Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Blood Glucose/analysis; Cytoplasmic and Nuclear/*physiology; Fatty Liver/*drug therapy/metabolism; Gene Expression Regulation; Genetic; Inbred C57BL; Lipid Metabolism; Liver/metabolism; Male; Mice; Non-alcoholic Fatty Liver Disease; PPAR gamma/*genetics; Receptors; Repressor Proteins/genetics; Retinoic Acid Receptor alpha; Retinoic Acid/physiology; Transcription; Tretinoin/pharmacology/*therapeutic use
Creator
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Kim Seong-Chul; Kim Chun-Ki; Axe David; Cook Aaron; Lee Mikang; Li Tiangang; Smallwood Nicole; Chiang John Y L; Hardwick James P; Moore David D; Lee Yoon-Kwang
Description
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UNLABELLED: Mice deficient in small heterodimer partner (SHP) are protected from diet-induced hepatic steatosis resulting from increased fatty acid oxidation and decreased lipogenesis. The decreased lipogenesis appears to be a direct consequence of very low expression of peroxisome proliferator-activated receptor gamma 2 (PPAR-gamma2), a potent lipogenic transcription factor, in the SHP(-/-) liver. The current study focused on the identification of a SHP-dependent regulatory cascade that controls PPAR-gamma2 gene expression, thereby regulating hepatic fat accumulation. Illumina BeadChip array (Illumina, Inc., San Diego, CA) and real-time polymerase chain reaction were used to identify genes responsible for the linkage between SHP and PPAR-gamma2 using hepatic RNAs isolated from SHP(-/-) and SHP-overexpressing mice. The initial efforts identify that hairy and enhancer of split 6 (Hes6), a novel transcriptional repressor, is an important mediator of the regulation of PPAR-gamma2 transcription by SHP. The Hes6 promoter is specifically activated by the retinoic acid receptor (RAR) in response to its natural agonist ligand, all-trans retinoic acid (atRA), and is repressed by SHP. Hes6 subsequently represses hepatocyte nuclear factor 4 alpha (HNF-4alpha)-activated PPAR-gamma2 gene expression by direct inhibition of
Identifier
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<a href="http://doi.org/10.1002/hep.26699" target="_blank" rel="noreferrer noopener">10.1002/hep.26699</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).
2014
Animals
Axe David
Basic Helix-Loop-Helix Transcription Factors/genetics
Blood Glucose/analysis
Chiang John Y L
Cook Aaron
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Fatty Liver/*drug therapy/metabolism
Gene Expression Regulation
Genetic
Hardwick James P
Hepatology (Baltimore, Md.)
Inbred C57BL
Kim Chun-Ki
Kim Seong-Chul
Lee Mikang
Lee Yoon-Kwang
Li Tiangang
Lipid Metabolism
Liver/metabolism
Male
Mice
Moore David D
NEOMED College of Medicine
NEOMED College of Pharmacy
Non-alcoholic Fatty Liver Disease
PPAR gamma/*genetics
Receptors
Repressor Proteins/genetics
Retinoic Acid Receptor alpha
Retinoic Acid/physiology
Smallwood Nicole
Transcription
Tretinoin/pharmacology/*therapeutic use