1
40
4
-
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>
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
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
Humans; Male; Animals; Mice; *Atherosclerosis; *Farnesoid X receptor; *NAFLD; *Obesity; *TGR5; Diet; Hep G2 Cells; Receptors; Inbred C57BL; High-Fat/adverse effects; Cytoplasmic and Nuclear/*agonists; Bile Acids and Salts/pharmacology/*therapeutic use; Hypercholesterolemia/*drug therapy/etiology/metabolism; Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism; Obesity/*drug therapy/etiology/metabolism; G-Protein-Coupled/*agonists
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>
*Atherosclerosis
*Farnesoid X receptor
*NAFLD
*Obesity
*TGR5
2018
Adorini Luciano
Animals
Bile Acids and Salts/pharmacology/*therapeutic use
Cytoplasmic and Nuclear/*agonists
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Diet
G-Protein-Coupled/*agonists
Hep G2 Cells
High-Fat/adverse effects
Humans
Hypercholesterolemia/*drug therapy/etiology/metabolism
Inbred C57BL
Jadhav Kavita
Kasumov Takhar
Lee Yoon Kwang
Li Yuanyuan
Male
Mice
Molecular metabolism
NEOMED College of Medicine
NEOMED College of Pharmacy
Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism
Obesity/*drug therapy/etiology/metabolism
Receptors
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.pharmthera.2017.07.008" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.pharmthera.2017.07.008</a>
Pages
22–33
Volume
181
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
Stable isotope-based flux studies in nonalcoholic fatty liver disease.
Publisher
An entity responsible for making the resource available
Pharmacology & therapeutics
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-01
Subject
The topic of the resource
*Citric acid cycle; *Fatty acid oxidation; *Fibrosis; *NAFLD; *Oxidative stress; *Stable isotopes; Animals; Humans; Isotopes/metabolism; Mass Spectrometry/*methods; Non-alcoholic Fatty Liver Disease/*metabolism
Creator
An entity primarily responsible for making the resource
McCullough Arthur; Previs Stephen; Kasumov Takhar
Description
An account of the resource
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression. This review focuses mainly on the utilization of mass spectrometry-based methods for the understanding of metabolic abnormalities in the different stages of NAFLD. For example, stable isotope-based flux studies demonstrated multi-organ insulin resistance, dysregulated glucose, lipids and lipoprotein metabolism in patients with NAFLD. We also review recent developments in the stable isotope-based technologies for the study of mitochondrial dysfunction, oxidative stress and fibrogenesis in NAFLD. We highlight the limitations of current methodologies, discuss the emerging areas of research in this field, and future directions for the applications of stable isotopes to study NAFLD and its complications.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.pharmthera.2017.07.008" target="_blank" rel="noreferrer noopener">10.1016/j.pharmthera.2017.07.008</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).
*Citric acid cycle
*Fatty acid oxidation
*Fibrosis
*NAFLD
*Oxidative Stress
*Stable isotopes
2018
Animals
Department of Pharmaceutical Sciences
Humans
Isotopes/metabolism
Kasumov Takhar
Mass Spectrometry/*methods
McCullough Arthur
NEOMED College of Pharmacy
Non-alcoholic Fatty Liver Disease/*metabolism
Pharmacology & therapeutics
Previs Stephen
-
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.freeradbiomed.2016.03.032" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.freeradbiomed.2016.03.032</a>
Pages
13–21
Volume
96
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 Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.
Publisher
An entity responsible for making the resource available
Free radical biology & medicine
Date
A point or period of time associated with an event in the lifecycle of the resource
2016
2016-07
Subject
The topic of the resource
*Flux; *Glutathione; *Heavy water; *Mass spectrometer; *NAFLD; *NASH; *Oxidative stress; *Western Diet; Animal; Animals; Antioxidants/metabolism; Diet; Disease Models; Glutathione/blood/*metabolism; Humans; LDL/blood/*genetics/metabolism; Liver/*metabolism/pathology; Mice; Non-alcoholic Fatty Liver Disease/blood/*genetics/pathology; Oxidative Stress/genetics; Receptors; Western/adverse effects
Creator
An entity primarily responsible for making the resource
Li Ling; Zhang Guo-Fang; Lee Kwangwon; Lopez Rocio; Previs Stephen F; Willard Belinda; McCullough Arthur; Kasumov Takhar
Description
An account of the resource
Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepatic glutathione metabolism in patients with NAFLD. As a primary source of plasma glutathione, liver plays an important role in interorgan glutathione homeostasis. In this study, we have tested the hypothesis that measurements of plasma glutathione turnover could be used to assess the hepatic glutathione metabolism in LDLR(-/)(-) mice, a mouse model of diet-induced NAFLD. Mice were fed a standard low fat diet (LFD) or a high fat diet containing cholesterol (a Western type diet (WD)). The kinetics of hepatic and plasma glutathione were quantified using the (2)H2O metabolic labeling approach. Our results show that a WD leads to reduced fractional synthesis rates (FSR) of hepatic (25%/h in LFD vs. 18%/h in WD, P\textless0.05) and plasma glutathione (43%/h in LFD vs. 21%/h in WD, P\textless0.05), without any significant effect on their absolute production rates (PRs). WD-induced concordant changes in both hepatic and plasma glutathione turnover suggest that the plasma glutathione turnover measurements could be used to assess hepatic glutathione metabolism. The safety, simplicity, and low cost of the (2)H2O-based glutathione turnover approach suggest that this method has the potential for non-invasive probing of hepatic glutathione metabolism in patients with NAFLD and other diseases.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.freeradbiomed.2016.03.032" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2016.03.032</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).
*Flux
*Glutathione
*Heavy water
*Mass spectrometer
*NAFLD
*NASH
*Oxidative Stress
*Western Diet
2016
Animal
Animals
Antioxidants/metabolism
Department of Pharmaceutical Sciences
Diet
Disease Models
Free radical biology & medicine
Glutathione/blood/*metabolism
Humans
Kasumov Takhar
LDL/blood/*genetics/metabolism
Lee Kwangwon
Li Ling
Liver/*metabolism/pathology
Lopez Rocio
McCullough Arthur
Mice
NEOMED College of Pharmacy
Non-alcoholic Fatty Liver Disease/blood/*genetics/pathology
Oxidative Stress/genetics
Previs Stephen F
Receptors
Western/adverse effects
Willard Belinda
Zhang Guo-Fang