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

Thiamine: A Natural Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) Activator Parasuraman Aiya Subramani https://orcid.org/0000-0002-7394-5174 Firdose Begum Shaik R. Dinakaran Michael https://orcid.org/0000-0002-8105-745X Kalpana Panati https://orcid.org/0000-0002-0829-0917 Venkata Ramireddy Narala https://orcid.org/0000-0001-6672-4165 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-γ) is a ligand-activated transcription factor etiologically relevant to T2D. We hypothesized that thiamine could be a PPAR-γ ligand and thus activate PPAR-γ and ameliorate T2D.
Objective:

This study aims to establish thiamine as a PPAR-γ ligand via molecular docking and dynamics simulations (MDS) and thiamine’s ability to induce adipogenesis while upregulating PPAR-γ and AP-2 genes using in vitro assays.
Methods:

Thiamine/PPAR-γ binding was studied using Schrödinger’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-γ 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-γ. MDS indicate that the interactions between thiamine and PPAR-γ 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-γ. Thiamine treatment significantly increases the mRNA levels of PPAR-γ and AP-2 genes.
Conclusion:

Our results show that thiamine is a PPAR-γ ligand. Animal studies and clinical trials are required to corroborate the results obtained.
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