CMHX008, a PPARγ partial agonist, enhances insulin sensitivity with minor influences on bone loss

Publication date: Available online 6 June 2018Source: Genes & DiseasesAuthor(s): Yi Hou, Xuemei Cao, Xiangnan Hu, Xinyu Li, Xiaoqin Shi, Hongying Wang, Chuan Peng, Jiayu Li, Jibin Li, Qifu Li, Chaodong Wu, Xiaoqiu XiaoAbstractTraditional thiazolidinediones (TZDs), such as rosiglitazone, are peroxisome proliferator-activated receptor γ (PPARγ) potent agonists that can be used to treat type 2 diabetes but carry unwanted effects, including increased risk for fracture. The present work aimed to compare the insulin-sensitizing efficacies and bone-loss side effects of CMHX008, a novel TZDs-like PPARγ partial agonist, with those of rosiglitazone. A TR-FRET PPARγ competitive binding assay was used to compare the binding affinity between CMHX008 and rosiglitazone. Mice were administered vehicle, CMHX008 or rosiglitazone for 16 weeks. Mesenchymal stem cells (MSCs) were used to examine differences in differentiation into osteoblasts after compounds treatment. TR-FRET showed lower affinity to PPARγ by CMHX008 compared with rosiglitazone. Mice treated with CMHX008 showed insulin sensitization similar to that of mice treated with rosiglitazone, which was related to the significant inhibition of PPARγ Ser273 phosphorylation and improved insulin sensitivity by facilitating the phosphorylation of insulin receptor and Akt in adipose tissues. Micro-CT and histomorphometric analyses demonstrated that the degree of trabecular bone loss after treatment with CMHX008 was weaker than that obser...
Source: Genes and Diseases - Category: Genetics & Stem Cells Source Type: research