Compelling evidence shows that NLRP3 (the most studied member of the NLR family) activation by DAMPs (generated by nutrient excess in obesity) plays a key role behind the chronic inflammation characteristic of obesity and IR (Stienstra et al., 2010, 2011, 2012; Zhou et al., 2010; Koenen et al., 2011; Vandanmagsar et al., 2011; Lee et al., 2013). Here, NLRP3 is linked to obesity due to melanocortin 4 receptor deficiency.