Description
Full activation of peroxisome proliferator-activated receptor γ (PPARγ), e.g., using thiazolidinediones, effectively treats insulin resistance and type 2 diabetes but also commonly promotes weight gain, hyperphagia, and edema. GQ-16 is a partial agonist for PPARγ (Ki = 160 nM) which induces adipogenesis significantly less than the full activator rosiglitazone. Like rosiglitazone, GQ-16 reverses high fat diet-mediated impairments in insulin signaling. However, GQ-16 does not induce weight gain, hyperphagia, or edema. GQ-16 does not activate PPARα, PPARβ/δ, or RXRα.
in vitro
gq-16 was an effective inhibitor of cdk5-mediated phosphorylation of pparγ, exhibiting a ki value of 160 nm. gq-16 was specific for pparγ and possessed no detectable activity when tested for the ability to activate other ppar subtypes (pparα or pparβ/δ) or rxrα. in both nih-3t3 and c3h10t1/2 cell models with established pparγ-dependent adipogenesis, gq-16 displayed reduced the potential of adipogenic [1].
in vivo
in the mouse model of diet-induced obesity and insulin resistance, administration of gq-16 (20 mg/kg/day) by oral gavage daily blocked hfd-dependent effects on intracellular inflammatory pathways and improved insulin sensitivity. gq-16 did not elicit increased weight gain [1].
References
[1] amato a a, rajagopalan s, lin j z, et al. gq-16, a novel peroxisome proliferator-activated receptor γ (pparγ) ligand, promotes insulin sensitization without weight gain[j]. journal of biological chemistry, 2012, 287(33): 28169-28179.
