Thiamine: A Natural Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) Activator

Background: There has been increasing evidence of the correlation between thiamine deficiency and type 2 diabetes (T2D). T2D is a condition in which an individual's insulin sensitivity is highly compromised. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-activated transcription factor etiologically relevant to T2D. We hypothesized that thiamine could be a PPAR-gamma ligand and thus activate PPAR-gamma and ameliorate T2D. Objective: This study aims to establish thiamine as a PPAR-gamma ligand via molecular docking and dynamics simulations (MDS) and thiamine's ability to induce adipogenesis while upregulating PPAR-gamma and AP-2 genes using in vitro assays. Methods: Thiamine/PPAR-gamma binding was studied using Schrodinger's Glide. The bound complex was simulated in the OPLS 2005 force field using Desmond. 3T3-L1 preadipocyte cells were differentiated in the presence of thiamine and rosiglitazone and stained with Oil Red O. Nuclear protein from the differentiated cells was used to study the binding of the PPAR-gamma response element (PPRE) using an ELISA-based assay. mRNA from differentiated cells was used to study the expression of genes using quantitative RTPCR. Results: In silico docking shows that thiamine binds with PPAR-gamma. MDS indicate that the interactions between thiamine and PPAR-gamma are stable over a significant period. Thiamine induces the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner and enhances the PPRE-binding activity of PPAR-gamma. Thiamine treatment significantly increases the mRNA levels of PPAR-gamma and AP-2 genes. Conclusion: Our results show that thiamine is a PPAR-gamma ligand. Animal studies and clinical trials are required to corroborate the results obtained.

Automated summary

This study establishes thiamine as a PPAR-gamma ligand through molecular docking and dynamics simulations. In vitro assays show that thiamine induces adipogenesis and upregulates the expression of PPAR-gamma and AP-2 genes. Animal studies and clinical trials are necessary to confirm these findings.