SR 202 is a selective PPARγ antagonist which attenuates troglitazone-induced PPARγ transcriptional activity with IC50 value of 140μM. It inhibits PPARγ-dependent adipocyte differentiation and growth in vitro and in vivo and improves insulin sensitivity in diabetic ob/ob mice and increases HDL levels in rats in vivo.
PPARγ is expressed predominantly in adipose tissue, where it is known to play a critical role in adipocyte differentiation and fat deposition. Its synthetic ligands, the thiazolidinediones (TZD), are used as insulin sensitizers in the treatment of type 2 diabetes. SR-202 is a selective PPARγ antagonist, which is able to antagonize TZD-induced transcriptional activity of PPAR γ with an IC50 of 140 μM. In preadipocyte 3T3-L1 cells, treatment with SR-202 at different concentrations for 24h was able to significantly inhibit BRL 49653- and hormone-induced adipocyte differentiation of 3T3-L1 cells in a dose-dependent manner. The antiadipogenic effect of SR-202 was also revealed by the reduced expression of an adipocyte differentiation marker, the adipocyte fatty acid binding protein (aP2). In vivo, wild-type (wt) mice treated with SR-202 for 10 wk gained significantly less body weight than untreated wt mice under both SD (standard diet) and HFD (high fat diet). Consistent with this result, the treatment of wt mice by SR-202 significantly decreased WAT (white adipose tissue) mass under SD and protected them from HFD-induced increase in WAT mass. Moreover, treating PPAR/mice with SR-202 further decreased plasma levels of leptin and TNFα under HFD, whereas only leptin was further decreased under SD[1].
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