TitleFatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells.
Publication TypeJournal Article
Year of Publication2002
AuthorsPawar, A, Xu, J, Jerks, E, Mangelsdorf, DJ, Jump, DB
JournalJ Biol Chem
Volume277
Issue42
Pagination39243-50
Date Published2002 Oct 18
ISSN0021-9258
KeywordsCell Line, Cell Nucleus, Cell-Free System, Chromatography, High Pressure Liquid, DNA-Binding Proteins, Dose-Response Relationship, Drug, Fatty Acids, Fatty Acids, Unsaturated, Gene Expression Regulation, Enzymologic, Genetic Vectors, Humans, Lipid Metabolism, Liver X Receptors, Orphan Nuclear Receptors, Plasmids, Protein Binding, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Time Factors, Transcription Factors, Transfection
Abstract

 

Fatty acids bind to and regulate the activity of peroxisome proliferator-activated (PPAR) and liver X receptors (LXR). However, the role lipid metabolism plays in the control of intracellular fatty acid ligands is poorly understood. We have identified two strains of HEK293 cells that display differences in fatty acid regulation of nuclear receptors. Using full-length and Gal4-LBD chimeric receptors in functional assays, 20:4,n6 induced PPARalpha activity approximately 2.2-fold and suppressed LXRalpha activity by 80% (ED50 approximately 25-50 microm) in HEK293-E (early passage) cells but had no effect on PPARalpha or LXRalpha receptor activity in HEK293-L (late passage) cells. LXRbeta was insensitive to fatty acid regulation in both HEK293 strains. Metabolic labeling studies using [14C]20:4,n6 (at 100 microm) indicated that the uptake of 20:4,n6 and its assimilation into triacylglycerol, diacylglycerol, and polar lipids revealed no difference between the two strains. Such treatment increased total cellular 20:4,n6 ( approximately 11-fold) and its elongation product, 22:4,n6 ( approximately 3.6-fold), within 6 h. Non-esterified 20:4,n6 and 22:4,n6 represented
DOI10.1074/jbc.M206170200
Alternate JournalJ. Biol. Chem.
PubMed ID12161442
Grant ListR01 DK043220 / DK / NIDDK NIH HHS / United States
DK43220 / DK / NIDDK NIH HHS / United States