To test whether conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevents age-associated weight gain and diet-induced obesity, we created conditional Sirt1 knock-in (KI) mice based on the Rosa26 system [28], crossed with Pomc-Cre mice [29] or Agrp-Cre mice [30], and analysed the effect of Sirt1 overexpression in POMC neurons or AgRP neurons. Here, AGRP is linked to obesity due to melanocortin 4 receptor deficiency.