1
40
14
-
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/10.1038/nature10111" target="_blank" rel="noreferrer noopener">http://doi.org/10.1038/nature10111</a>
Pages
506–510
Issue
7352
Volume
474
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
A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.
Publisher
An entity responsible for making the resource available
Nature
Date
A point or period of time associated with an event in the lifecycle of the resource
2011
2011-06-23
Subject
The topic of the resource
BILE acids; HOMEOSTASIS; HYPOGLYCEMIC agents; INSULIN resistance; LABORATORY mice; LECITHIN; TRIGLYCERIDES
Creator
An entity primarily responsible for making the resource
Lee Jae Man; Lee Yoon-Kwang; Mamrosh Jennifer L; Busby Scott A; Griffin Patrick R; Pathak Manish C; Ortlund Eric A; Moore David D
Description
An account of the resource
Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis. [ABSTRACT FROM AUTHOR]
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1038/nature10111" target="_blank" rel="noreferrer noopener">10.1038/nature10111</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).
2011
BILE acids
Busby Scott A
Department of Integrative Medical Sciences
Griffin Patrick R
Homeostasis
HYPOGLYCEMIC agents
Insulin Resistance
LABORATORY mice
LECITHIN
Lee Jae Man
Lee Yoon-Kwang
Mamrosh Jennifer L
Moore David D
Nature
NEOMED College of Medicine
Ortlund Eric A
Pathak Manish C
triglycerides
-
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/10.2174/1874467208666150817112109" target="_blank" rel="noreferrer noopener">http://doi.org/10.2174/1874467208666150817112109</a>
Pages
226–236
Issue
3
Volume
10
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
Signal Transduction Mechanisms of Alcoholic Fatty Liver Disease: Emer ging Role of Lipin-1.
Publisher
An entity responsible for making the resource available
Current molecular pharmacology
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
1905-7
Subject
The topic of the resource
Humans; Animals; AMP-Activated Protein Kinases/metabolism; Signal Transduction; Lipid Metabolism; Fatty Liver; Liver/metabolism; lipid metabolism; alcoholic fatty liver disease; inflammation; Lipin-1; signal transduction; transcriptional regulators; Phosphatidate Phosphatase/*metabolism; Inflammation/metabolism; Ethanol/chemistry/*metabolism; Sirtuin 1/metabolism; Alcoholic/*metabolism/pathology
Creator
An entity primarily responsible for making the resource
You Min; Jogasuria Alvin; Lee Kwangwon; Wu Jiashin; Zhang Yanqiao; Lee Yoon-Kwang; Sadana Prabodh
Description
An account of the resource
Lipin-1, a mammalian phosphatidic acid phosphatase (PAP), is a bi-functional molecule involved in various signaling pathways via its function as a PAP enzyme in the triglyceride synthesis pathway and in the nucleus as a transcriptional co-regulator. In the liver, lipin-1 is known to play a vital role in controlling the lipid metabolism and inflammation process at multiple regulatory levels. Alcoholic fatty liver disease (AFLD) is one of the earliest forms of liver injury and approximately 8-20% of patients with simple steatosis can develop into more severe forms of liver injury, including steatohepatitis, fibrosis/ cirrhosis, and eventually hepatocellular carcinoma (HCC). The signal transduction mechanisms for alcohol-induced detrimental effects in liver involves alteration of complex and multiple signaling pathways largely governed by a central and upstream signaling system, namely, sirtuin 1 (SIRT1)-AMP activated kinase (AMPK) axis. Emerging evidence suggests a pivotal role of lipin-1 as a crucial downstream regulator of
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.2174/1874467208666150817112109" target="_blank" rel="noreferrer noopener">10.2174/1874467208666150817112109</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).
2017
alcoholic fatty liver disease
Alcoholic/*metabolism/pathology
AMP-Activated Protein Kinases/metabolism
Animals
Current molecular pharmacology
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Ethanol/chemistry/*metabolism
Fatty Liver
Humans
Inflammation
Inflammation/metabolism
Jogasuria Alvin
Lee Kwangwon
Lee Yoon-Kwang
Lipid Metabolism
Lipin-1
Liver/metabolism
NEOMED College of Graduate Studies
NEOMED College of Medicine
NEOMED College of Pharmacy
Phosphatidate Phosphatase/*metabolism
Sadana Prabodh
Signal Transduction
Sirtuin 1/metabolism
transcriptional regulators
Wu Jiashin
You Min
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/10.1194/jlr.M069013" target="_blank" rel="noreferrer noopener">http://doi.org/10.1194/jlr.M069013</a>
Pages
1541–1551
Issue
8
Volume
57
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
Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.
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
2016
2016-08
Subject
The topic of the resource
*estrogen; *estrogen receptor alpha; *lipid and lipoprotein metabolism; *small heterodimer partner; *triglycerides; *very low density lipoprotein; Animals; Cholesterol Ester Transfer Proteins/*physiology; Estrogen Receptor alpha/metabolism; Estrogens/physiology; Female; Inbred C57BL; Lipid Metabolism; Liver/*metabolism; Metabolic Networks and Pathways; Mice; Oxidation-Reduction; Transgenic; Triglycerides/biosynthesis/*blood
Creator
An entity primarily responsible for making the resource
Palmisano Brian T; Le Thao D; Zhu Lin; Lee Yoon-Kwang; Stafford John M
Description
An account of the resource
Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver beta-oxidation and reduced liver TG content by 60%. Liver estrogen receptor alpha (ERalpha) was required for CETP expression to enhance beta-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERalpha to enhance beta-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1194/jlr.M069013" target="_blank" rel="noreferrer noopener">10.1194/jlr.M069013</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).
*estrogen
*estrogen receptor alpha
*lipid and lipoprotein metabolism
*small heterodimer partner
*triglycerides
*very low density lipoprotein
2016
Animals
Cholesterol Ester Transfer Proteins/*physiology
Department of Integrative Medical Sciences
Estrogen Receptor alpha/metabolism
Estrogens/physiology
Female
Inbred C57BL
Journal of lipid research
Le Thao D
Lee Yoon-Kwang
Lipid Metabolism
Liver/*metabolism
Metabolic Networks and Pathways
Mice
NEOMED College of Medicine
Oxidation-Reduction
Palmisano Brian T
Stafford John M
Transgenic
Triglycerides/biosynthesis/*blood
Zhu Lin
-
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/10.1186/s12929-015-0133-3" target="_blank" rel="noreferrer noopener">http://doi.org/10.1186/s12929-015-0133-3</a>
Pages
30–30
Volume
22
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
The orphan nuclear receptor small heterodimer partner is required for thiazolidinedione effects in leptin-deficient mice.
Publisher
An entity responsible for making the resource available
Journal of biomedical science
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015-05
Subject
The topic of the resource
Animals; Bile Acids and Salts/metabolism; Cytoplasmic and Nuclear/biosynthesis/*genetics/metabolism; Diabetes Mellitus/*drug therapy/genetics/metabolism; Gene Expression Regulation/drug effects; Glucose/metabolism; Hepatocytes/drug effects; Humans; Insulin Resistance/genetics; Insulin/*metabolism; Leptin/deficiency/genetics; Lipid Metabolism/drug effects; Messenger/genetics; Mice; Obese; PPAR gamma/*biosynthesis/genetics; Receptors; RNA; Thiazolidinediones/*administration & dosage
Creator
An entity primarily responsible for making the resource
Tseng Hsiu-Ting; Park Young Joo; Lee Yoon-Kwang; Moore David D
Description
An account of the resource
BACKGROUND: Small heterodimer partner (SHP, NR0B2) is involved in diverse metabolic pathways, including hepatic bile acid, lipid and glucose homeostasis, and has been implicated in effects on the peroxisome proliferator-activated receptor gamma (PPARgamma), a master regulator of adipogenesis and the receptor for antidiabetic drugs thiazolidinediones (TZDs). In this study, we aim to investigate the role of SHP in TZD response by comparing TZD-treated leptin-deficient (ob/ob) and leptin-, SHP-deficient (ob/ob;Shp(-/-)) double mutant mice. RESULTS: Both ob/ob and double mutant ob/ob;Shp(-/-) mice developed hyperglycemia, insulin resistance, and hyperlipidemia, but hepatic fat accumulation was decreased in the double mutant ob/ob;Shp(-/-) mice. PPARgamma2 mRNA levels were markedly lower in ob/ob;Shp(-/-) liver and decreased to a lesser extent in adipose tissue. The TZD troglitazone did not reduce glucose or circulating triglyceride levels in ob/ob;Shp(-/-) mice. Expression of the adipocytokines, such as adiponectin and resistin, was not stimulated by troglitazone treatment. Expression of hepatic lipogenic genes was also reduced in ob/ob;Shp(-/-) mice. Moreover, overexpression of SHP by adenovirus infection increased PPARgamma2 mRNA levels in mouse primary hepatocytes. CONCLUSIONS: Our results suggest that SHP is required for both antidiabetic and hypolipidemic effects of TZDs in ob/ob mice through regulation of PPARgamma expression.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1186/s12929-015-0133-3" target="_blank" rel="noreferrer noopener">10.1186/s12929-015-0133-3</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 Acids and Salts/metabolism
Cytoplasmic and Nuclear/biosynthesis/*genetics/metabolism
Department of Integrative Medical Sciences
Diabetes Mellitus/*drug therapy/genetics/metabolism
Gene Expression Regulation/drug effects
Glucose/metabolism
Hepatocytes/drug effects
Humans
Insulin Resistance/genetics
Insulin/*metabolism
Journal of biomedical science
Lee Yoon-Kwang
Leptin/deficiency/genetics
Lipid Metabolism/drug effects
Messenger/genetics
Mice
Moore David D
NEOMED College of Medicine
Obese
Park Young Joo
PPAR gamma/*biosynthesis/genetics
Receptors
RNA
Thiazolidinediones/*administration & dosage
Tseng Hsiu-Ting
-
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/10.1152/ajpgi.00343.2015" target="_blank" rel="noreferrer noopener">http://doi.org/10.1152/ajpgi.00343.2015</a>
Pages
G799–807
Issue
10
Volume
310
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
Enhanced ethanol catabolism in orphan nuclear receptor SHP-null mice.
Publisher
An entity responsible for making the resource available
American journal of physiology. Gastrointestinal and liver physiology
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-05
Subject
The topic of the resource
*acetaldehyde dehydrogenase; *alcoholic fatty liver disease; *inflammation; *small heterodimer partner; Acetates/blood; Alcoholic/genetics/*metabolism; Aldehyde Dehydrogenase; Animals; Cytoplasmic and Nuclear/deficiency/*genetics/metabolism; Ethanol/blood/*metabolism/toxicity; Inbred C57BL; Lipid Peroxidation; Liver Diseases; Liver/drug effects/metabolism; Male; Mice; Mitochondrial/genetics/metabolism; PPAR gamma/genetics/metabolism; Receptors
Creator
An entity primarily responsible for making the resource
Park Jung Eun; Lee Mikang; Mifflin Ryan; Lee Yoon-Kwang
Description
An account of the resource
Deficiency of the orphan nuclear hormone receptor small heterodimer partner (SHP, NR0B2) protects mice from diet-induced hepatic steatosis, in part, via repression of peroxisome proliferator-activated receptor (PPAR)-gamma2 (Pparg2) gene expression. Alcoholic fatty liver diseases (AFLD) share many common pathophysiological features with non-AFLD. To study the role of SHP and PPARgamma2 in AFLD, we used a strategy of chronic ethanol feeding plus a single binge ethanol feeding to challenge wild-type (WT) and SHP-null (SHP(-/-)) mice with ethanol. The ethanol feeding induced liver fat accumulation and mRNA expression of hepatic Pparg2 in WT mice, which suggests that a high level of PPARgamma2 is a common driving force for fat accumulation induced by ethanol or a high-fat diet. Interestingly, ethanol-fed SHP(-/-) mice displayed hepatic fat accumulation similar to that of ethanol-fed WT mice, even though their Pparg2 expression level remained lower. Mortality of SHP(-/-) mice after ethanol binge feeding was significantly reduced and their acetaldehyde dehydrogenase (Aldh2) mRNA level was higher than that of their WT counterparts. After an intoxicating dose of ethanol, SHP(-/-) mice exhibited faster blood ethanol clearance and earlier wake-up time than WT mice. Higher blood acetate, the end product of ethanol metabolism, and lower acetaldehyde levels were evident in the ethanol-challenged SHP(-/-) than WT mice. Ethanol-induced inflammatory responses and lipid peroxidation were also lower in SHP(-/-) mice. The current data show faster ethanol catabolism and extra fat storage through conversion of acetate to acetyl-CoA before its release into the circulation in this ethanol-feeding model in SHP(-/-) mice.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1152/ajpgi.00343.2015" target="_blank" rel="noreferrer noopener">10.1152/ajpgi.00343.2015</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).
*acetaldehyde dehydrogenase
*alcoholic fatty liver disease
*Inflammation
*small heterodimer partner
2016
Acetates/blood
Alcoholic/genetics/*metabolism
Aldehyde Dehydrogenase
American journal of physiology. Gastrointestinal and liver physiology
Animals
Cytoplasmic and Nuclear/deficiency/*genetics/metabolism
Department of Integrative Medical Sciences
Ethanol/blood/*metabolism/toxicity
Inbred C57BL
Lee Mikang
Lee Yoon-Kwang
Lipid Peroxidation
Liver Diseases
Liver/drug effects/metabolism
Male
Mice
Mifflin Ryan
Mitochondrial/genetics/metabolism
NEOMED College of Medicine
Park Jung Eun
PPAR gamma/genetics/metabolism
Receptors
-
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/10.1124/dmd.115.064758" target="_blank" rel="noreferrer noopener">http://doi.org/10.1124/dmd.115.064758</a>
Pages
1002–1007
Issue
7
Volume
43
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
Farnesoid X Receptor Agonist Represses Cytochrome P450 2D6 Expression by Upregulating Small Heterodimer Partner.
Publisher
An entity responsible for making the resource available
Drug metabolism and disposition: the biological fate of chemicals
Date
A point or period of time associated with an event in the lifecycle of the resource
2015
2015-07
Subject
The topic of the resource
Animals; Cytochrome P-450 CYP2D6/*biosynthesis; Cytochrome P-450 Enzyme Inhibitors/*pharmacology; Cytoplasmic and Nuclear/*agonists; Enzymologic/drug effects; Gene Expression Regulation; Genetic/drug effects/genetics; HEK293 Cells; Hepatocytes/drug effects/enzymology/metabolism; Humans; Isoxazoles/*pharmacology; Knockout; Mice; Receptors; Transcription; Transgenic
Creator
An entity primarily responsible for making the resource
Pan Xian; Lee Yoon-Kwang; Jeong Hyunyoung
Description
An account of the resource
Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme responsible for eliminating approximately 20% of marketed drugs. Studies have shown that differential transcriptional regulation of CYP2D6 may contribute to large interindividual variability in CYP2D6-mediated drug metabolism. However, the factors governing CYP2D6 transcription are largely unknown. We previously demonstrated small heterodimer partner (SHP) as a novel transcriptional repressor of CYP2D6 expression. SHP is a representative target gene of the farnesoid X receptor (FXR). The objective of this study is to investigate whether an agonist of FXR,
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1124/dmd.115.064758" target="_blank" rel="noreferrer noopener">10.1124/dmd.115.064758</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
Cytochrome P-450 CYP2D6/*biosynthesis
Cytochrome P-450 Enzyme Inhibitors/*pharmacology
Cytoplasmic and Nuclear/*agonists
Department of Integrative Medical Sciences
Drug metabolism and disposition: the biological fate of chemicals
Enzymologic/drug effects
Gene Expression Regulation
Genetic/drug effects/genetics
HEK293 Cells
Hepatocytes/drug effects/enzymology/metabolism
Humans
Isoxazoles/*pharmacology
Jeong Hyunyoung
Knockout
Lee Yoon-Kwang
Mice
NEOMED College of Medicine
Pan Xian
Receptors
Transcription
Transgenic
-
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.molmet.2018.01.005" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.molmet.2018.01.005</a>
Pages
131–140
Volume
9
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
Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR.
Publisher
An entity responsible for making the resource available
Molecular metabolism
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-03
Subject
The topic of the resource
*Atherosclerosis; *Farnesoid X receptor; *NAFLD; *Obesity; *TGR5
Creator
An entity primarily responsible for making the resource
Jadhav Kavita; Xu Yang; Xu Yanyong; Li Yuanyuan; Xu Jiesi; Zhu Yingdong; Adorini Luciano; Lee Yoon-Kwang; Kasumov Takhar; Yin Liya; Zhang Yanqiao
Description
An account of the resource
OBJECTIVES: Activation of the bile acid (BA) receptors farnesoid X receptor (FXR) or G protein-coupled bile acid receptor (GPBAR1; TGR5) improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. METHODS: Wild-type (WT), Tgr5(-/-), Fxr(-/-), Apoe(-/-) and Shp(-/-) mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. RESULTS: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (CEBPalpha) as novel
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.molmet.2018.01.005" target="_blank" rel="noreferrer noopener">10.1016/j.molmet.2018.01.005</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).
*Atherosclerosis
*Farnesoid X receptor
*NAFLD
*Obesity
*TGR5
2018
Adorini Luciano
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Jadhav Kavita
Kasumov Takhar
Lee Yoon-Kwang
Li Yuanyuan
Molecular metabolism
NEOMED College of Medicine
NEOMED College of Pharmacy
Xu Jiesi
Xu Yang
Xu Yanyong
Yin Liya
Zhang Yanqiao
Zhu Yingdong
-
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.bmcl.2016.11.053" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bmcl.2016.11.053</a>
Pages
303–308
Issue
2
Volume
27
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
Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator.
Publisher
An entity responsible for making the resource available
Bioorganic & medicinal chemistry letters
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-01
Subject
The topic of the resource
*Diabetes; *High-fat diet; *Homology modeling; *Hyperlipidemia; *Lipoprotein lipase; *Liver cirrhosis; *Obesity; Animals; Benzeneacetamides/chemical synthesis/chemistry/*pharmacology; Dose-Response Relationship; Drug; Imidazoles/chemical synthesis/chemistry/*pharmacology; Lipoprotein Lipase/*metabolism; Mice; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship
Creator
An entity primarily responsible for making the resource
Geldenhuys Werner J; Caporoso Joel; Leeper Thomas C; Lee Yoon-Kwang; Lin Li; Darvesh Altaf S; Sadana Prabodh
Description
An account of the resource
Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist. We found that the cyclopropyl moiety of C10d is not absolutely necessary for LPL activity. Several substitutions were found to result in loss of LPL activity. The compound C10d was also tested in vivo for its lipid lowering activity. Mice were fed a high-fat diet (HFD) for four months, and treated for one week at 10mg/kg. At this dose, C10d exhibited in vivo biological activity as indicated by lower TG and cholesterol levels as well as reduced body fat content as determined by ECHO-MRI. Furthermore, C10d also reduced the HFD induced fat accumulation in the liver. Our study has provided insights into the structural and functional characteristics of this novel LPL activator.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bmcl.2016.11.053" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2016.11.053</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).
*Diabetes
*High-fat diet
*Homology modeling
*Hyperlipidemia
*Lipoprotein lipase
*Liver cirrhosis
*Obesity
2017
Animals
Benzeneacetamides/chemical synthesis/chemistry/*pharmacology
Bioorganic & medicinal chemistry letters
Caporoso Joel
Darvesh Altaf S
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Department of Pharmacy Practice
Dose-Response Relationship
Drug
Geldenhuys Werner J
Imidazoles/chemical synthesis/chemistry/*pharmacology
Lee Yoon-Kwang
Leeper Thomas C
Lin Li
Lipoprotein Lipase/*metabolism
Mice
Molecular Docking Simulation
Molecular Structure
NEOMED College of Graduate Studies
NEOMED College of Medicine
NEOMED College of Pharmacy
Sadana Prabodh
Structure-Activity Relationship
-
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.bbalip.2009.05.004" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.bbalip.2009.05.004</a>
Pages
991–996
Issue
10
Volume
1791
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
Forkhead box transcription factor O1 inhibits cholesterol 7alpha-hydroxylase in human hepatocytes and in high fat diet-fed mice.
Publisher
An entity responsible for making the resource available
Biochimica et biophysica acta
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
2009-10
Subject
The topic of the resource
Adenoviridae/genetics; Animals; Bile Acids and Salts/biosynthesis; Cell Line; Cell Nucleus/drug effects/metabolism; Cholesterol 7-alpha-Hydroxylase/*antagonists & inhibitors/genetics/metabolism; Dietary Fats/*administration & dosage/*pharmacology; Down-Regulation/drug effects; Enzymologic/drug effects; Feeding Behavior/*drug effects; Forkhead Box Protein O1; Forkhead Transcription Factors/genetics/*metabolism; Gene Expression Regulation; Gene Knockdown Techniques; Gene Transfer Techniques; Hepatocytes/drug effects/*enzymology; Humans; Inbred C57BL; Insulin Resistance; Insulin/metabolism; Male; Messenger/genetics/metabolism; Mice; RNA; RNA Interference/drug effects; Tumor
Creator
An entity primarily responsible for making the resource
Li Tiangang; Ma Huiyan; Park Young Joo; Lee Yoon-Kwang; Strom Stephen; Moore David D; Chiang John Y L
Description
An account of the resource
The conversion of cholesterol to bile acids is the major pathway for cholesterol catabolism. Bile acids are metabolic regulators of triglycerides and glucose metabolism in the liver. This study investigated the roles of FoxO1 in the regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression in primary human hepatocytes. Adenovirus-mediated expression of a phosphorylation defective and constitutively active form of FoxO1 (FoxO1-ADA) inhibited CYP7A1 mRNA expression and bile acid synthesis, while siRNA knockdown of FoxO1 resulted in a approximately 6-fold induction of CYP7A1 mRNA in human hepatocytes. Insulin caused rapid exclusion of FoxO1 from the nucleus and resulted in the induction of CYP7A1 mRNA expression, which was blocked by FoxO1-ADA. In high fat diet-fed mice, CYP7A1 mRNA expression was repressed and inversely correlated to increase hepatic FoxO1 mRNA expression and FoxO1 nuclear retention. In conclusion, our current study provides direct evidence that FoxO1 is a strong repressor of CYP7A1 gene expression and bile acid synthesis. Impaired regulation of FoxO1 may cause down-regulation of CYP7A1 gene expression and contribute to dyslipidemia in insulin resistance.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.bbalip.2009.05.004" target="_blank" rel="noreferrer noopener">10.1016/j.bbalip.2009.05.004</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).
2009
Adenoviridae/genetics
Animals
Bile Acids and Salts/biosynthesis
Biochimica et biophysica acta
Cell Line
Cell Nucleus/drug effects/metabolism
Chiang John Y L
Cholesterol 7-alpha-Hydroxylase/*antagonists & inhibitors/genetics/metabolism
Department of Integrative Medical Sciences
Dietary Fats/*administration & dosage/*pharmacology
Down-Regulation/drug effects
Enzymologic/drug effects
Feeding Behavior/*drug effects
Forkhead Box Protein O1
Forkhead Transcription Factors/genetics/*metabolism
Gene Expression Regulation
Gene Knockdown Techniques
Gene Transfer Techniques
Hepatocytes/drug effects/*enzymology
Humans
Inbred C57BL
Insulin Resistance
Insulin/metabolism
Lee Yoon-Kwang
Li Tiangang
Ma Huiyan
Male
Messenger/genetics/metabolism
Mice
Moore David D
NEOMED College of Medicine
Park Young Joo
RNA
RNA Interference/drug effects
Strom Stephen
Tumor
-
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/B978-0-12-404717-4.00005-6" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/B978-0-12-404717-4.00005-6</a>
Pages
157–266
Volume
66
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
Eicosanoids in metabolic syndrome.
Publisher
An entity responsible for making the resource available
Advances in pharmacology (San Diego, Calif.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2013
1905-7
Subject
The topic of the resource
Adipose Tissue; Animals; Eicosanoids/*metabolism; Fatty Liver/etiology/immunology/metabolism; Humans; Immune System/immunology/metabolism; Lipid Metabolism; Metabolic Syndrome/complications/immunology/*metabolism/physiopathology; Non-alcoholic Fatty Liver Disease; Obesity/complications/immunology/metabolism; Sepsis/complications/immunology/metabolism; White/immunology/metabolism
Creator
An entity primarily responsible for making the resource
Hardwick James P; Eckman Katie; Lee Yoon-Kwang; Abdelmegeed Mohamed A; Esterle Andrew; Chilian William M; Chiang John Y; Song Byoung-Joon
Description
An account of the resource
Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism. The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/B978-0-12-404717-4.00005-6" target="_blank" rel="noreferrer noopener">10.1016/B978-0-12-404717-4.00005-6</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
Abdelmegeed Mohamed A
Adipose Tissue
Advances in pharmacology (San Diego, Calif.)
Animals
Chiang John Y
Chilian William M
Department of Integrative Medical Sciences
Eckman Katie
Eicosanoids/*metabolism
Esterle Andrew
Fatty Liver/etiology/immunology/metabolism
Hardwick James P
Humans
Immune System/immunology/metabolism
Lee Yoon-Kwang
Lipid Metabolism
Metabolic Syndrome/complications/immunology/*metabolism/physiopathology
NEOMED College of Medicine
Non-alcoholic Fatty Liver Disease
Obesity/complications/immunology/metabolism
Sepsis/complications/immunology/metabolism
Song Byoung-Joon
White/immunology/metabolism
-
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/hep4.1120" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep4.1120</a>
Pages
1085–1098
Issue
10
Volume
1
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
Hairy and enhancer of split 6 prevents hepatic lipid accumulation through inhibition of Pparg2 expression.
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
2017
2017-12
Creator
An entity primarily responsible for making the resource
Park Jung Eun; Lee Mikang; Kim Seong-Chul; Zhang Yanqiao; Hardwick James P; Lee Yoon-Kwang
Description
An account of the resource
Peroxisome proliferator-activated receptor gamma (PPARgamma) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPARgamma2 isoform reprograms liver for lipid storage and causes abnormal fat accumulation in certain pathophysiologic conditions. The current study aimed to investigate a role of transcriptional repressor hairy and enhancer of split 6 (HES6) in the regulation of Pparg2 expression and hepatic steatosis induced by diet. Liver-specific overexpression of Hes6 using adenovirus reduced Pparg2 messenger RNA levels by 90% and hepatic triglyceride accumulation by 22% compared to the levels in mice injected with an adenoviral empty vector with Western diet feeding. In sharp contrast, silencing Hes6 gene expression using short hairpin RNA increased hepatic lipid accumulation and Pparg2 messenger RNA levels by 70% and 4-fold, respectively. To locate hepatocyte nuclear factor 4 alpha (HNF4alpha) binding site(s), through which repressional activity of HES6 is mediated, a 2.5-kb Pparg2 promoter-driven luciferase reporter was constructed for transient transfection assays. Subsequently, chromatin immunoprecipitation and electrophoretic mobility shift assays were performed. An HNF4alpha binding consensus sequence was identified at 903 base pairs upstream from the transcription start site of Pparg2. Deletion or point mutation of the sequence in a luciferase reporter containing the Pparg2 promoter abolished HNF4alpha-mediated activation in HeLa cells. Chromatin immunoprecipitation and electrophoretic mobility shift assays further confirmed direct recruitment and binding of HNF4alpha to the site. Gene expression analysis with liver samples from subjects with nonalcoholic steatohepatitis suggested that the axis of the Hes6-Hnf4a-Pparg2 transcriptional cascade is also responsible for hepatic fat accumulation in humans. Conclusion: HES6 represses Pparg2 gene expression, thereby preventing hepatic lipid accumulation induced by chronic Western diet feeding or pathophysiologic conditions. (Hepatology Communications 2017;1:1085-1098).
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep4.1120" target="_blank" rel="noreferrer noopener">10.1002/hep4.1120</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).
2017
Department of Integrative Medical Sciences
Hardwick James P
Hepatology communications
Kim Seong-Chul
Lee Mikang
Lee Yoon-Kwang
NEOMED College of Medicine
Park Jung Eun
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/10.1002/hep.29305" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.29305</a>
Pages
1854–1865
Issue
6
Volume
66
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
Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice.
Publisher
An entity responsible for making the resource available
Hepatology (Baltimore, Md.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-12
Subject
The topic of the resource
Animals; Body Weight/genetics; Cytoplasmic and Nuclear/*physiology; Diabetes Mellitus; Fatty Liver/*genetics; Knockout; Lipid Metabolism/genetics; Mice; Receptors; Type 2/*genetics
Creator
An entity primarily responsible for making the resource
Akinrotimi Oludemilade; Riessen Ryan; VanDuyne Philip; Park Jung Eun; Lee Yoon-Kwang; Wong Lee-Jun; Zavacki Ann M; Schoonjans Kristina; Anakk Sayeepriyadarshini
Description
An account of the resource
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr (-/-) Shp(-/-) double knockout (DKO) mice are refractory to weight gain, glucose intolerance, and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice were also very active and that correlated well with the observed increase in phosphoenolpyruvate carboxykinase expression, type IA fibers, and mitochondrial function in skeletal muscle. Mechanistically, we demonstrate that liver-specific Shp deletion protects against fatty liver development by suppressing expression of peroxisome proliferator-activated receptor gamma 2 and lipid-droplet protein fat-specific protein 27 beta. CONCLUSION: These data suggest that Fxr and Shp inactivation may be beneficial to combat diet-induced obesity and uncover that hepatic SHP is necessary to promote fatty liver disease. (Hepatology 2017;66:1854-1865).
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep.29305" target="_blank" rel="noreferrer noopener">10.1002/hep.29305</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).
2017
Akinrotimi Oludemilade
Anakk Sayeepriyadarshini
Animals
Body Weight/genetics
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
Diabetes Mellitus
Fatty Liver/*genetics
Hepatology (Baltimore, Md.)
Knockout
Lee Yoon-Kwang
Lipid Metabolism/genetics
Mice
NEOMED College of Medicine
Park Jung Eun
Receptors
Riessen Ryan
Schoonjans Kristina
Type 2/*genetics
VanDuyne Philip
Wong Lee-Jun
Zavacki Ann M
-
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/hep.28712" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.28712</a>
Pages
1072–1085
Issue
4
Volume
64
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
Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice.
Publisher
An entity responsible for making the resource available
Hepatology (Baltimore, Md.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-10
Subject
The topic of the resource
*Intestinal Absorption; Animals; Bile Acids and Salts/*chemistry; Biological Transport; Cholesterol/*metabolism; Cytoplasmic and Nuclear/*physiology; Inbred C57BL; Mice; Receptors
Creator
An entity primarily responsible for making the resource
Xu Yang; Li Fei; Zalzala Munaf; Xu Jiesi; Gonzalez Frank J; Adorini Luciano; Lee Yoon-Kwang; Yin Liya; Zhang Yanqiao
Description
An account of the resource
UNLABELLED: Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7alpha-hydroxylase (Cyp7a1) and sterol 12alpha-hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and altered bile acid composition, with the alpha/beta-muricholic acid proportion in bile increased by 2.6-fold and taurocholic acid (TCA) level reduced by 71%. Overexpression of Cyp8b1 or concurrent overexpression of Cyp7a1 and Cyp8b1 normalizes TCA level, bile acid composition, and intestinal cholesterol absorption. CONCLUSION: Activation of FXR inhibits intestinal cholesterol absorption by modulation of bile acid pool size and composition, thus leading to increased RCT. Targeting hepatic FXR and/or bile acids may be useful for boosting RCT and preventing the development of atherosclerosis. (Hepatology 2016;64:1072-1085).
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep.28712" target="_blank" rel="noreferrer noopener">10.1002/hep.28712</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).
*Intestinal Absorption
2016
Adorini Luciano
Animals
Bile Acids and Salts/*chemistry
Biological Transport
Cholesterol/*metabolism
Cytoplasmic and Nuclear/*physiology
Department of Integrative Medical Sciences
Gonzalez Frank J
Hepatology (Baltimore, Md.)
Inbred C57BL
Lee Yoon-Kwang
Li Fei
Mice
NEOMED College of Medicine
Receptors
Xu Jiesi
Xu Yang
Yin Liya
Zalzala Munaf
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/10.1002/hep.26699" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.26699</a>
Pages
1750–1760
Issue
5
Volume
59
Dublin Core
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
All-trans-retinoic acid ameliorates hepatic steatosis in mice by a novel transcriptional cascade.
Publisher
An entity responsible for making the resource available
Hepatology (Baltimore, Md.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2014
2014-05
Subject
The topic of the resource
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
An entity primarily responsible for making the resource
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
An account of the resource
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
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/hep.26699" target="_blank" rel="noreferrer noopener">10.1002/hep.26699</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).
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