INS and obesity due to melanocortin 4 receptor deficiency: 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).