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Title:Peroxisome Proliferator -Activated Receptor (Ppar)alpha Regulation of Highly Unsaturated Fatty Acid Synthesis
Author(s):Li, Yue
Doctoral Committee Chair(s):Nakamura, Manabu T.
Department / Program:Food Science and Human Nutrition
Discipline:Food Science and Human Nutrition
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Health Sciences, Nutrition
Abstract:The aim of the subsequent study was to identify a PPARalpha ligand under EFA deficiency. Lysophospholipids (lysoPL) are the most likely candidates for the ligands because decreased HUFA under EFA deficiency may shift the equilibrium of phospholipid deacylation/reacylation cycle toward accumulation of lysoPL. To test the hypothesis, first we used computer simulation to estimate affinity between lysoPL and PPARalpha. The model predicted lysoPL binding with high affinity. Next, binding affinity of lysoPL to PPARalpha was measured in vitro using a fluorescent ligand displacement assay. The dissociation constants (Kd) of lysoPL were low nanomolar suggesting that they are potent ligands for PPARalpha. Finally, when CV-1 cells were treated with lysoPL, a reporter plasmid with PPARalpha response elements was induced. In conclusion, our study suggests that PPARalpha, together with SREBP-1c, senses HUFA status and confers pathway specific induction of HUFA synthesis by EFA deficient diets. LysoPL may act as signaling molecule and activate PPARalpha in response to essential fatty acid deficiency.
Issue Date:2006
Type:Text
Language:English
Description:94 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006.
URI:http://hdl.handle.net/2142/83704
Other Identifier(s):(MiAaPQ)AAI3242920
Date Available in IDEALS:2015-09-25
Date Deposited:2006


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