Uncoupling protein 1 (UCP1) is a classical feature of brown adipocytes and understanding its regulatory mechanism will help in the development of a pharmacological approach for obesity and associated metabolic diseases. The epigenetic regulation of UCP1 in brown adipocytes is not completely understood. Our study is focused on histone deacetylases (HDACs), which are set of enzymes that bring about changes in gene expression pattern by changing the histone acetylation status. Our data suggest that inhibition of Class-I HDACs can increase the expression of UCP1 in brown and white adipocytes; whereas inhibition of Class-II HDACs can decrease the UCP1 expression in brown adipocytes. Thus, by pharmacologically targeting specific HDAC enzymes, it might be possible to modulate UCP1 expression and thermogenic function in brown and white adipocytes. This will help burning excessive energy in the form of heat and in turn promote reduction of body weight, alleviate obesity and associated metabolic diseases.