A novel dual peroxisome proliferator-activated receptors alpha and gamma agonist with beneficial effects on insulin resistance and lipid metabolism.
Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key regulators of lipid homeostasis and insulin resistance. In this study we show that a novel compound, 3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}- 2-[2-(2-nitro-phenoxy)-acetyl amino]-propionic acid (O325H), is an agonist with dual effect on PPARalpha/gamma by using dual-luciferase reporter gene assay. By activating PPARalpha and PPARgamma simultaneously, O325H promotes pre-adipocyte differentiation and up-regulates the expression of glucose and lipid metabolic target genes. In diabetic mice, administration of O325H at 10 mg/kg decreases the blood lipid and glucose levels. Therefore, O325H has dual action on PPARalpha and PPARgamma and is a promising agent for the amelioration of lipid metabolic disorders and diabetes associated with insulin resistance.
Xu
Cheng
C
Pharmaceutical university of Shenyang, Shenyang, China.
Wang
Li-Li
LL
Liu
Hong-Ying
HY
Ruan
Cheng-Mai
CM
Zhou
Xing-Bo
XB
Cao
Ying-Lin
YL
Li
Song
S
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation; D048909:Diabetes Complications / Q000188:drug therapy*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D023421:Models, Animal; D010080:Oxazoles / Q000494:pharmacology*; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
C515729:3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)-2-(2-(2-nitrophenoxy)acetylamino)propionic acid; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D014443:Tyrosine