A collection of recent studies have identified the NLRP3 inflammasome as a central sensor that detects obesity-related stress signals and that triggers IL-1β production and subsequent disease pathogenesis (Masters et al., 2010; Stienstra et al., 2010, 2011; Vandanmagsar et al., 2011; Wen et al., 2011; Henao-Mejia et al., 2012). Here, NLRP3 is linked to obesity due to melanocortin 4 receptor deficiency.