Role of CMHX003，a novel peroxisome proliferator-activated receptor γ selective partial agonist in enhancing insulin sensitivity in 3T3-L1 cells

Abstract:

Objective：To investigate the effect of CMHX003，a novel peroxisome proliferator-activated receptor γ（PPARγ） selective partial agonist，on the enhancement of insulin sensitivity in 3T3-L1 preadipocytes. Methods：PPARγ agonist activity was determined by using luci-ferase reporter gene assay. 3T3-L1 preadipocytes were differentiated into adipocytes according to standard protocols. Oil red O staining was performed at the end of differentiation and the adiponectin and aP2 mRNA levels were detected by real-time PCR. The secreted adiponectin levels in the culture medium were measured with mouse adiponectin ELISA kit. Results：The result of luciferase reporter assay suggested that PPARγ agonist activity of CMHX003 was higher than that of rosiglitazone（2.46±0.08，3.31±0.15，F=132.19，P=0.008）. CMHX003 had weaker role in promoting 3T3-L1 preadipocyte differentiation and triglyceride accu－mulation than rosiglitazone but similar role in increasing expression and secretion of adiponectin（59.41±3.01，107.91±16.49， χ2=9.031，P=0.112）（74.61±16.94，140.07±30.67， χ2=9.051，P=0.135） as rosiglitazone. Meanwhile，CMHX003 was less likely to increase aP2 expression（3.07±1.86，75.95±26.04， χ2=8.868，P=0.049）. Conclusions：CMHX003 may potentially be developed into an effective and safe agent in the treatment of type 2 diabetes mel－litus and metabolic disorders.