To elucidate the pathways downstream of SIRT1 activation responsible for the observed efficacy in these in vivo models, we performed Causal Network Modeling (CNM) of gene expression data from livers of mice fed a high fat diet (diet-induced obesity, DIO) and treated with SIRT1 activators, SRT501 (1000 mg/kg, oral dosing) or SRT1720 (100 mg/kg, oral dosing) for three days (Figure 1). This evidence concerns the gene SIRT1 and obesity due to melanocortin 4 receptor deficiency.