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The role of peroxisome proliferator-activated receptor gamma coactivator 1 beta in human hepatocyte lipid composition, secretion, and beta oxidation
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Johnson, Diana. The role of peroxisome proliferator-activated receptor gamma coactivator 1 beta in human hepatocyte lipid composition, secretion, and beta oxidation. Retrieved from https://doi.org/doi:10.7282/T3862G6W

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TitleThe role of peroxisome proliferator-activated receptor gamma coactivator 1 beta in human hepatocyte lipid composition, secretion, and beta oxidation
NameJohnson, Diana (author); Dixon, Joseph L (chair); Igal, Ariel (internal member); Storch, Judith (internal member); Brasaemle, Dawn (internal member); Buckley, Brian (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2010
Other Date2010-10 (degree)
SubjectNutritional Sciences, Lipids--Metabolism, Hepatocyte growth factor, Mitochondria--Formation
Extentxx, 213 p. : ill.
DescriptionThe 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.
NotePh.D.
NoteIncludes bibliographical references
NoteIncludes vita
Noteby Diana Roshek Johnson
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3862G6W
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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