Uses
L-165,041 has been used as a peroxisome proliferator-activated receptor β/δ (PPARβ/δ) ligand to study its influence on PPARβ/δ mediated postnatal myogenesis in C2C12 myoblasts.
Definition
ChEBI: 2-[4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid is an aromatic ketone.
General Description
A cell-permeable phenoxyacetic acid derivative that acts as a potent and selective peroxisome proliferator activator receptor δ (PPARδ) agonist (Ki = 6 nM for hPPARδ and 730 nM for hPPARγ). Potently induces adipocyte differentiation in NIH-PPARδ cells at 500 nM and raises total cholesterol in insulin resistant db/db mice without altering glucose or triglycerides levels. Increases UCP3 (uncoupling protein 3) gene expression in L6 myotubes. Inhibits cytokine-induced expression of VCAM-1 (vascular cell adhesion molecule-1) and the secretion of MCP-1 (monocyte chemotactic protein-1) in EAhy926 cells.
Biological Activity
Potent PPAR δ agonist (K i = 6 nM); displays > 100-fold selectivity for both mouse and human PPAR δ ? receptors over other subtypes. In vivo, raises plasma cholesterol levels in insulin-resistant db/db mice and is neuroprotective in models of cerebral infarction and Parkinson's disease.
Biochem/physiol Actions
Cell permeable: yes
in vitro
l-165041, which is a selective and potent pparδligand, displayed in this specified transactivation system, apart from its highly efficacious pparδ agonist activity, partial and full agonism at, respectively, pparγ2 and pparαsubtypes [1].
in vivo
l-165041 could drastically reduce lipid accumulation in the mouse liver, decreasing total hepatic triglyceride and cholesterol content compared to the vehicle group. gene analysis demonstrated that l-165041 lowered hepatic expression of pparγ, apolipoprotein b, il-1β, and interleukin-6. in contrast, l-165041 increased hepatic expressions of pparδ, lipoprotein lipase, and atp-binding cassette transporter g1 (abcg1) [2].
References
[1] wurch t, junquero d, delhon a, pauwels j. pharmacological analysis of wild-type alpha, gamma and delta subtypes of the human peroxisome proliferator-activated receptor. naunyn schmiedebergs arch pharmacol. 2002 feb;365(2):133-40.
[2] lim hj, park jh, lee s, choi he, lee ks, park hy. ppardelta ligand l-165041 ameliorates western diet-induced hepatic lipid accumulation and inflammation in ldlr-/- mice. eur j pharmacol. 2009 nov 10;622(1-3):45-51.
