While inflammasome formation and pyroptotic cell death are critical for fighting infection and also contribute to inflammation in diseases including type II diabetes, obesity, and atherosclerosis (Kuemmerle-Deschner et al., 2011; Wen et al., 2011; 2012), the signals that trigger caspase-1 activation remain poorly understood. Here, CASP1 is linked to obesity due to melanocortin 4 receptor deficiency.