Acta Pharmacologica Sinica 2006 February; 27 (2): 223-228; doi: 10.1111/j.1745-7254.2006.00263.x

Aim: To examine the effects of novel peroxisome proliferator-activated receptor (PPAR) a/g dual agonist C333H on insulin resistance and lipid metabolism.

Methods: An established dual-luciferase reporter gene assay system was used in vitro to test the activity of C333H with respect to the transcription of human PPARa and PPARg. A preadipocyte differentiation assay and reverse transcription-polymerase chain reaction were used to detect the functional activities of C333H. In db/db mice, the effects of C333H were investigated with respect to lowering of blood glucose and lipid levels.

Results: C333H was determined to be a novel PPARa/g dual agonist because it strongly induced luciferase activity on human PPARa and PPARg, promoting the differentiation of preadipocytes to adipocytes, and functioning in upregulating the expression of some glucose and lipid metabolic target genes of the PPAR. In addition, C333H efficiently reduced blood lipid and glucose concentrations in db/db diabetic mice.

Conclusion: C333H has dual action on both PPARa and PPARg, and might be of interest for the amelioration of lipid metabolic disorders and insulin resistance associated with type 2 diabetes.

Keywords: C333H; peroxisome proliferator-activated receptor; insulin resistance; lipid metabolism; diabetes