RRC ID 18992
Author Yokoi H, Mizukami H, Nagatsu A, Tanabe H, Inoue M.
Title Hydroxy monounsaturated fatty acids as agonists for peroxisome proliferator-activated receptors.
Journal Biol Pharm Bull
Abstract The physiological and pathological role of oxidized polyunsaturated fatty acids (PUFAs) has been extensively studied, whereas those of hydroxy monounsaturated fatty acids (MUFAs) are not well understood. This study demonstrated that 11-hydroxy-(9Z)-octadecenoic acid ((9Z)-11-HOE), which was isolated from adlay seeds (Coix lacryma-jobi L. var. ma-yuen STAF.), can activate peroxisome proliferator-activated receptor (PPAR)alpha, delta and gamma in luciferase reporter assays more efficiently than (9Z)-octadecenoic acid (oleic acid), and to the same degree as linoleic acid. (9Z)-11-HOE increased the mRNA levels of UCP2 and CD36 in C2C12 myotubes and THP- 1 cells, respectively, and these effects were blocked by the PPARdelta- and gamma-specific antagonists GSK0660 and T0070907, respectively. Evaluation of the structure.activity relationship between hydroxy MUFAs and PPAR activation revealed that (9E)-11-HOE, the geometrical isomer of (9Z)-11-HOE, activated PPARs more potently than (9Z)-11-HOE, and that PPAR activation by hydroxyl MUFAs was not markedly influenced by the position of the hydroxy group or the double bond, although PPARdelta seemed to possess ligand specificity different to that of PPARalpha or gamma . Additionally, the finding that 11-hydroxy octadecanoic acid, the hydrogenated product of (9E)-11- HOE, was also capable of activating PPARs to a similar extent as (9E)-11-HOE indicates that the double bond in hydroxy MUFAs is not essential for PPAR activation. In conclusion, (9Z)-11-HOE derived from alday seeds and hydroxy MUFAs with a chain length of 16 or 18 acted as PPAR agonists. Hydroxylation of MUFAs may change these compounds from silent PPAR ligands to active PPAR agonists.
Volume 33(5)
Pages 854-61
Published 2010
DOI 10.1248/bpb.33.854
PII JST.JSTAGE/bpb/33.854
PMID 20460766
MeSH Animals CD36 Antigens / genetics CD36 Antigens / metabolism Cell Line Coix / chemistry* Fatty Acids, Monounsaturated / chemistry Fatty Acids, Monounsaturated / isolation & purification Fatty Acids, Monounsaturated / pharmacology* Fatty Acids, Unsaturated / metabolism Gene Expression / drug effects* Hepatocytes Humans Hydrogenation Ion Channels / genetics Ion Channels / metabolism Isomerism Ligands Lipid Metabolism / genetics* Male Mice Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Muscle Fibers, Skeletal / metabolism PPAR gamma / antagonists & inhibitors Peroxisome Proliferator-Activated Receptors / agonists* Plant Oils / isolation & purification Plant Oils / pharmacology* RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Seeds / chemistry Structure-Activity Relationship Transcriptional Activation / drug effects* Uncoupling Protein 2
IF 1.54
Times Cited 21
Human and Animal Cells C2C12 (RCB0987) 293 (RCB1637) THP-1 (RCB1189)