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The role of peroxisome proliferator-activated receptor gamma coactivator 1 beta in human hepatocyte lipid composition, secretion, and beta oxidation
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
The role of peroxisome proliferator-activated receptor gamma coactivator 1 beta in human hepatocyte lipid composition, secretion, and beta oxidation
Identifier
ETD_2933
Identifier
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http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056422
Language
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eng
Genre
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theses
Subject
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(authority = RUETD)
Topic
Nutritional Sciences
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Lipids--Metabolism
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Hepatocyte growth factor
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Mitochondria--Formation
Abstract
(type = abstract)
The Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Beta (PGC1β) is a nuclear transcription factor coactivator that is involved in lipogenesis, very low density lipoprotein (VLDL) formation and secretion, and mitochondrial biogenesis. When PGC1β is over-expressed in mouse liver, there is a dramatic increase in the plasma VLDL; which is interesting because mice usually do not have much VLDL in their plasma. PGC1β knock out mice have lower plasma triglycerides, but also have problems with mitochondrial biogenesis and cold adaptation. The goal of this research project is to identify the mechanism by which PGC1β contributes to the lipid metabolism in human liver HepG2 cells. This project was done by creating an adenovirus for PGC1β expression and studying the changes in lipid metabolism in HepG2 cells and lipids secreted to the culture medium. Over-expression of PGC1β in HepG2 cells caused significant decrease in the mass of neutral lipids: monoglycerides, diglycerides, triglycerides, and cholesteryl esters. There were no significant differences in the masses of any phospholipid species. This was evident both in the culture medium of cells and in the hepatoma liver cells. This phenotype was not corrected by incubating the cells with excess fatty acid. When [14C]-oleic acid was added to the cells, cells that over-expressed PGC1β had significant decreases in triglyceride and cholesteryl ester synthesis, and a significant increase in phospholipid synthesis. This was an interesting finding considering that the total masses of the phospholipids were unchanged. PGC1β over-expressing cells have an increased ability to oxidize lipids by β-oxidation. To examine lipid composition of the lipid classes, the lipids were analyzed by liquid chromatography mass spectrometry (LCMS). There were no major differences in the fatty acyl chains of any of the lipid species in PGC1β over-expressing cells. Over-expressing PGC1β caused a shift in HepG2 cells lipid metabolism away from triglyceride synthesis and into phospholipid synthesis. It also caused an upregulation in β-oxidation. Thus, PGC1β is an interesting drug target for hepatic steatosis or hyperlipidemia because PGC1β not only can increase lipid oxidation, but it also decreases neutral lipid synthesis.
PhysicalDescription
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electronic resource
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xx, 213 p. : ill.
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Note
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Ph.D.
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Includes bibliographical references
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Includes vita
Note
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by Diana Roshek Johnson
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Johnson
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Diana
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1978-
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author
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Diana Johnson
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Dixon
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Joseph L
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chair
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Advisory Committee
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Joseph L Dixon
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Igal
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Ariel
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internal member
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Advisory Committee
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Ariel Igal
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Storch
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Judith
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internal member
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Advisory Committee
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Judith Storch
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Brasaemle
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Dawn
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Dawn Brasaemle
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Buckley
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Brian
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outside member
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Advisory Committee
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Brian Buckley
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
OriginInfo
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2010
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2010-10
Place
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xx
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3862G6W
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Name
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Johnson
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Diana
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DateTime
2010-09-28 21:45:33
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Diana Johnson
Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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