CMHX008, a novel peroxisome proliferator-activated receptor partial agonist, enhances insulin sensitivity in vitro and in vivo. Academic Article uri icon


  • The peroxisome proliferator-activated receptor (PPAR) plays an important role in adipocyte differentiation and insulin sensitivity. Its ligand rosiglitazone has anti-diabetic effect but is frequently accompanied with some severe unwanted effects. The aim of the current study was to compare the anti-diabetic effect of CMHX008, a novel thiazolidinedione-derivative, with rosiglitazone. A luciferase assay was used to evaluate in vitro PPAR activation. 3T3-L1 cells were used to examine adipocyte differentiation. High fat diet (HFD) mice were used to examine in vivo insulin sensitivity. The mRNA levels were evaluated by real-time RT-PCR. Serum biochemical and hormonal variables were assessed using a clinical chemistry analyser. CMHX008 displayed a moderate PPAR agonist activity, and promoted 3T3-L1 preadipocyte differentiation with lower activity than rosiglitazone. CMHX008 regulated the expression of PPAR target genes in a different manner from rosiglitazone. CMHX008 increased the expression and secretion of adiponectin with the similar efficacy as rosiglitazone, but only 25% as potent as rosiglitazone for the induction of adipocyte fatty acid binding protein. Treatment of CMHX008 and rosiglitazone protected mice from high fat diet (HFD)-induced glucose intolerance, hyperinsulinemia and inflammation. CMHX008 reduced the mRNA expression of M1 macrophage markers, and significantly increased the expressions of M2 markers. In conclusion, CMHX008 shared the comparable insulin-sensitizing effects as rosiglitazone with lower adipogenic capacity and might potentially be developed into an effective agent for the treatment of diabetes and metabolic disorders.

published proceedings

  • PLoS One

author list (cited authors)

  • Ming, Y., Hu, X., Song, Y., Liu, Z., Li, J., Gao, R., ... Xiao, X.

citation count

  • 12

complete list of authors

  • Ming, Yue||Hu, Xiangnan||Song, Ying||Liu, Zhiguo||Li, Jibin||Gao, Rufei||Zhang, Yuyao||Mei, Hu||Guo, Tingwang||Xiao, Ling||Wang, Bochu||Wu, Chaodong||Xiao, Xiaoqiu

editor list (cited editors)

  • Müller, R.

publication date

  • July 2014