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40
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Text
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<a href="http://doi.org/10.1002/hep.31604" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.31604</a>
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ISSN
1527-3350 0270-9139
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<a href="http://neomed.idm.oclc.org/login?url=http://doi.org/10.1002/hep.31604" target="_blank" rel="noreferrer noopener">NEOMED Full-text Holding (if available) - Proxy DOI: 10.1002/hep.31604</a>
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October 2020 List
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NEOMED College of Medicine
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Department of Integrative Medical Sciences
NEOMED Postdoc Publications
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Title
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Hepatocyte nuclear factor 4α prevents the steatosis-to-NASH progression by regulating p53 and bile acid signaling.
Publisher
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Hepatology
Date
A point or period of time associated with an event in the lifecycle of the resource
2020
2020-10-23
Subject
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steatohepatitis; apoptosis; bile acid; HNF4α; lipolysis; P53
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Xu Y;Zhu Y;Hu S;Xu Y;Stroup D;Pan X;Bawa FC;Chen S;Gopoju R;Yin Liya;Zhang Y
Description
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Hepatocyte nuclear factor 4α (HNF4α) is highly enriched in the liver, but its role in the progression of liver steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) has not been elucidated. In this study, we investigated the effect of gain or loss of hepatocyte HNF4α function on the development and progression of non-alcoholic fatty liver disease (NAFLD) in mice. Over-expression of human HNF4α protected against high fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis whereas loss of hepatocyte Hnf4α had opposite effects. HNF4α prevented hepatic triglyceride accumulation by promoting hepatic triglyceride lipolysis, fatty acid oxidation and VLDL secretion. Furthermore, HNF4α suppressed the progression of NAFL to NASH. Over-expression of human HNF4α inhibited HFCF diet-induced steatohepatitis in control mice but not in hepatocyte-specific p53(-/-) mice. In HFCF diet-fed mice lacking hepatic Hnf4α, recapitulation of hepatic expression of HNF4α targets cholesterol 7α-hydroxylase and sterol 12α-hydroxylase normalized hepatic triglyceride levels and attenuated steatohepatitis. CONCLUSIONS: The current study indicates that hepatocyte HNF4α protects against diet-induced development and progression of NAFLD by coordinating the regulation of lipolytic, p53 and bile acid signaling pathways. Targeting hepatic HNF4α may be useful for treatment of NASH.
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<a href="http://doi.org/10.1002/hep.31604" target="_blank" rel="noreferrer noopener">10.1002/hep.31604</a>
Format
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journalArticle
2020
Apoptosis
Bawa FC
bile acid
Chen S
Department of Integrative Medical Sciences
Gopoju R
Hepatology
HNF4α
Hu S
journalArticle
Lipolysis
NEOMED College of Medicine
NEOMED College of Medicine Postdoc
NEOMED Postdoc Publications
October 2020 List
p53
Pan X
steatohepatitis
Stroup D
Xu Y
Yin Liya
Zhang Y
Zhu Y
-
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/10.1096/fasebj.2020.34.s1.09002" target="_blank" rel="noreferrer noopener">http://doi.org/10.1096/fasebj.2020.34.s1.09002</a>
Issue
S1
Volume
34
ISSN
0892-6638
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Locate full-text within NEOMED Library's e-journal collections
<a href="http://neomed.idm.oclc.org/login?url=http://doi.org/10.1096/fasebj.2020.34.s1.09002" target="_blank" rel="noreferrer noopener">NEOMED Full-text Holding (if available) - Proxy DOI: 10.1096/fasebj.2020.34.s1.09002</a>
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Update Year & Number
September 2020 List
NEOMED College
NEOMED College of Medicine Student
NEOMED College of Medicine
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NEOMED Student Publications
Department of Integrative Medical Sciences
NEOMED Postdoc Publications
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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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Retinoic acid receptor α signaling protects against diet‐induced hepatosteatosis and obesity in mice
Publisher
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Faseb Journal
Date
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2020
2020-04
Creator
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Bawa F;Xu Y;Zhu Y;Chen S;Gopoju R;Zhang Y
Description
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Nonalcoholic fatty liver disease (NAFLD) is often characterized by accumulation of lipids in the liver. It presents a pathological spectrum of changes from simple steatosis to steatohepatitis. It is also often associated with obesity and insulin resistance. Since liver is the main organ involved in retinoid signaling, the impairment of this pathway is shown to increase liver fibrosis with the activation of stellate cells which stores retinoids in liver. However, the role of the retinoid signaling in NAFLD and obesity is not fully understood. Some studies have shown that retinoic acid treatment can ameliorate insulin resistance and obesity. We hypothesize that Retinoic Acid Receptor α (RARα) in hepatocytes play a significant role in mediating retinoid signaling to protect against NAFLD and obesity. To address this hypothesis, we conducted in vivo studies using liver‐specific Rarα knockout mice. Rarα floxed mice were injected with AAV8‐TBG‐Cre or AAV8‐TBG‐Null to generate liver‐specific Rarα knockout mice (L‐Rarα−/−) mice and the control mice (Rarαfl/fl). These mice were gavaged with either vehicle or all‐trans retinoic acid (AtRA; 15mg/kg/day) along with high fat/high cholesterol/high fructose (HFCF) diet for 16 weeks. The data showed that AtRA treatment reduced body fat content and increased energy expenditure in the control mice but not in L‐Rarα−/− mice. In addition, AtRA reduced hepatic triglyceride (TG) levels in both the control mice and L‐Rarα−/− mice with a greater extent in reduction of hepatic TG levels in the control mice. Analysis of hepatic gene expression by qRT‐PCR showed that AtRA reduced hepatic levels of genes involved in lipogenesis and fatty acid uptake (Pparγ, Cd36 and L‐Fabp) or inflammation (Tnf‐α) in the control mice, but not in L‐RARα−/− mice. Similar observations were collected in a different study where control mice and L‐Rara−/− mice were fed an HFCF diet for 20 weeks, followed by 10 weeks of treatment with either vehicle or AtRA. Our data demonstrate that the retinoid signaling protects against the development of hepatosteatosis and obesity in a Rarα‐dependent manner.
Identifier
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<a href="http://doi.org/10.1096/fasebj.2020.34.s1.09002" target="_blank" rel="noreferrer noopener">10.1096/fasebj.2020.34.s1.09002</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).
Format
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journalArticle
2020
Bawa F
Chen S
Department of Integrative Medical Sciences
Faseb Journal
Gopoju R
journalArticle
NEOMED College of Medicine Student
NEOMED Postdoc Publications
NEOMED Student Publications
September 2020 List
Xu Y
Zhang Y
Zhu Y