Metformin and Pioglitazone Reduce Gene Expression of Inflammatory Factors in Insulin Resistant and Hypertrophied Adipocytes

Abstract

Objective: In obesity, chronic low grade inflammation, created by induction of pro-inflammatory markers, causes adipocyte dysfunction in adipose tissue. Adipocytes dysfunction is associated with various diseases including insulin resistance and obesity. In obesity, inflammatory factors such as osteopontin (OPN), angiopoietin-like protein 2 (Angptl2) and transforming growth factor-β (TGF-β) are induced in adipose tissue. Metformin and pioglitazone that are used to modulate inflammation, but the relevant mechanism is poorly understood. This study aimed to investigate the effect of metformin and pioglitazone as anti-diabetic drugs, on gene expression of osteopontin, Angptl2 and TGF-β as inflammatory factors in insulin resistance and hypertrophied adipocyte in 3T3-L1 cell line model in vitro.

Materials and Methods: In this experimental research, we differentiated3T3-L1 preadipocytes to adipocytes. The adipocytes treated in insulin resistance and hypertrophied conditions with metformin and pioglitazone and assayed gene expression of OPN, Angptl2 and TGF-β by Real-Time PCR. Data was analyzed by SPSS statistic software.

Results: The results showed that expression of OPN, Angptl2, and TGF-β were increased significantly over 2-fold (P-value< 0.05) in insulin resistance and hypertrophied adipocytes compared to normal adipocytes. Pre- and co-treatment with metformin and pioglitazone led to reduced expression of Angptl2 and TGF-β. Only metformin significantly reduced the expression of Angptl2, TGF-β and OPN in hypertrophied adipocyte.

Conclusion: These results support the proposal that metformin and pioglitazone reduce gene expression of inflammatory factors in insulin resistant and hypertrophied adipocytes.