NLRP3 and obesity due to melanocortin 4 receptor deficiency: For example, in murine high-fat diet models, deficiency in Nlrp3, Casp1/11, Asc, Il1b or Il1r protects mice from developing obesity and insulin resistance.14,15,27,28 Mechanistically, increased levels of IL-1β inhibits insulin signaling in adipocytes and hepatocytes, and induces pancreatic β-cell dysfunction.13 So while NLRP3 and IL-1β may perform beneficial functions in metabolic regulation in the steady-state, NLRP3 appears to respond aberrantly to excess, in this case excessive nutrients and/or dysfunctional mitochondria.