Peroxisome Proliferator -Activated Receptor (Ppar)alpha Regulation of Highly Unsaturated Fatty Acid Synthesis

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Food Science and Human Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Li, Yue

Contributors dc:contributor

• Nakamura, Manabu T.

• Health Sciences, Nutrition

Language dc:language

eng

Identifier

(MiAaPQ)AAI3242920

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/83704