[5-(3-Indol-1-ylpropoxy)-1H-indol-3-yl] Acetic Acid Enhances Adipocyte Differentiation and Glucose Uptake in 3T3-L1 Cells

Abstract

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an important role in adipocyte differentiation and is the target for anti-diabetic drugs known as thiazolidinediones. Here, we synthesized and characterized a new PPAR gamma agonist, SPA0432. COS-7 cells treated with SPA0432 showed significantly increased PPAR gamma transcriptional activity compared to that of vehicle-treated cells. However, its efficacy was less than that of rosiglitazone. Using a standard differentiation protocol, SPA0432 effectively enhanced differentiation of 3T3-L1 preadipocytes as evidenced by increased lipid droplet formation and triglyceride accumulation. Real-time RT-PCR analysis indicated that SPA0432 significantly increased the expressions of adipogenesis-related genes, CAAT/enhancer binding protein alpha, PPAR gamma, fatty acid synthase, aP2 and lipoprotein lipase and significantly decreased the expression of Pref-1, a preadipocyte marker. Moreover, SPA0432 increased insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. These results suggest that SAP0432 may exert beneficial effects against insulin resistance through its ability to promote adipocyte differentiation and insulin-stimulated glucose uptake.