DNA methyltransferase inhibition by 5-azacytidine promotes thermogenic programming in beige adipocytes

Beige adipocytes play a critical role in energy metabolism by promoting thermogenesis, a process largely influenced by epigenetic modifications such as DNA methylation. This study investigates the effect of DNA demethylation on beige adipocyte differentiation and function using 5-azacytidine (5-AzaC), a DNA methyltransferase inhibitor. We evaluated changes in adipogenic and thermogenic gene expression, mitochondrial activity, and fatty acid uptake following 5-AzaC treatment in 3T3-L1-derived beige adipocytes. Our findings indicate that 5-AzaC does not significantly affect adipocyte differentiation but enhances thermogenic gene expression, including Ucp1 and Cox7a1, and increases mitochondrial function and fatty acid uptake. These results suggest that DNA demethylation modulates beige adipocyte function and may have implications for metabolic disorders such as obesity and type 2 diabetes.