It has been reported that PPARγ deacetylation (K268 and K293) via SIRT1 upon long-term TZD treatment protected against diet-induced obesity by enhancing browning of white adipose tissue and increasing energy expenditure, thus uncouples the adverse effects of TZD in weight gain from insulin sensitization (50, 51). This evidence concerns the gene PPARG and obesity due to melanocortin 4 receptor deficiency.