Our results add NOD2 as an important PRR to the growing list of immune components that protect against dysbiosis and metabolic disease during obesity, which includes TLR2 (Caricilli et al, 2011), TLR5 (Vijay-Kumar et al, 2010), and inflammasome components (Henao-Mejia et al, 2012). Here, NOD2 is linked to obesity due to melanocortin 4 receptor deficiency.