RGD Reference Report - Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor alpha activity in rat primary hepatocytes. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor alpha activity in rat primary hepatocytes.

Authors: Pawar, A  Jump, DB 
Citation: Pawar A and Jump DB, J Biol Chem. 2003 Sep 19;278(38):35931-9. Epub 2003 Jul 9.
RGD ID: 1580225
Pubmed: PMID:12853447   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M306238200   (Journal Full-text)

Peroxisome proliferator-activated receptors (PPARs alpha, beta, gamma1, and gamma2) are widely regarded as monitors of intracellular nonesterified fatty acid (NEFA) levels. As such, fatty acid binding to PPAR leads to changes in the transcription of many genes involved in lipid metabolism and storage. Although the composition of the intracellular NEFA pool is likely an important factor controlling PPAR activity, little information is available on factors affecting its composition. Accordingly, we have examined the effects of exogenous fatty acids on PPARalpha activity and NEFA pool composition in rat primary hepatocytes. Prior to the addition of fatty acids to primary hepatocytes, nonesterified unsaturated fatty acid levels are very low, representing 22:6n-3 > 18:3n-3/6 = 20:5n-3. Of these fatty acids, only 20:5n-3 and 22:6n-3 consistently induced PPARalpha activity. Metabolic labeling of primary hepatocytes indicated that both 14C-18:1n-9 and 14C-20:5n-3 are rapidly assimilated into neutral and polar lipids. Although the addition of 18:1n-9 had no effect on NEFA pool composition, 20:5n-3 mass increased >15-fold within 90 min. Changes in NEFA pool 20:5n-3 mass correlated with dynamic changes in the PPARalpha-regulated transcript mRNACYP4A. Metabolic labeling also indicated that a significant fraction of 14C-20:5n-3 was elongated to 22:5n-3. Cells treated with 22:5n-3 or 22:6n-3 led to a significant accumulation of 20:5n-3 in the NEFA pool through a process that requires peroxisomal beta-oxidation and fatty acyl CoA thioesterase activity. Further analyses suggest that 20:5n-3 and 22:6n-3, but not 22:5n-3, are active ligands for PPARalpha. These studies suggest that basal fatty acid levels in the NEFA pool coupled with rates of fatty acid esterification, elongation, desaturation, peroxisomal beta-oxidation, and fatty acyl thioestease activity are important determinants controlling NEFA pool composition and PPARalpha activity.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PparaRatfatty acid metabolic process  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppara  (peroxisome proliferator activated receptor alpha)


Additional Information